http://repub.eur.nl/res/aut/334/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/26646/ 2011-11-01T00:00:00Z Objective: To assess the safety and efficacy of the Genous™ endothelial progenitor cell (EPC) capturing stent in conjunction with HmG-CoA-reductase inhibitors (statins) to stimulate EPC recruitment, in the treatment of patients with de novo coronary artery lesions. Methods and results: The HEALING IIB study was a multi-center, prospective trial, including 100 patients. The primary efficacy endpoint was late luminal loss by QCA at 6-month follow-up (FU). Although statin therapy increased relative EPC levels by 5.6-fold, the angiographic outcome at 6 month FU was not improved in patients with an overall in-stent late luminal loss of 0.76 ± 0.50 mm. The composite major adverse cardiac events (MACE) rate was 9.4%, whereas 6.3% clinically justified target lesion revascularizations (TLRs) were observed. 2 Patients died within the first 30 days after stent implantation due to angiographically verified in-stent thrombosis. At 12 month FU, MACE and TLR increased to 15.6% and 11.5% respectively and stabilized until 24 month FU. 18 Month angiographic FU showed a significant decrease in late luminal loss (0.67 ± 0.54, 11.8% reduction or 10% by matched serial analysis, P= 0.001). Conclusion: The HEALING IIB study suggests that statin therapy in combination with the EPC capture stent does not contribute to a reduction of in-stent restenosis formation for the treatment of de novo coronary artery disease. Although concomitant statin therapy was able to stimulate EPC recruitment, it did not improve the angiographic outcome of the bio-engineered EPC capture stent. Remarkably, angiographic late loss was significantly reduced between 6 and 18 months. http://repub.eur.nl/res/pub/34442/ 2011-11-01T00:00:00Z Objectives: The present analysis was performed to evaluate the impact of diabetes mellitus (DM) status on the severity of coronary artery disease (CAD) and current approaches in interventional treatment. Background: Little is known about the effect of DM treated with diet, oral agents, or insulin on lesion characteristics and anatomical pattern of CAD and their interventional treatment. Methods and results: Patients (n = 46,779) of the contemporary Euro Heart Survey PCI registry with known DM status were included in this analysis. Nondiabetics (n = 35,280, 75.4%) were compared with diabetics treated with diet (n = 1,533, 3.3%), oral agents (n = 7,222, 15.4%), and insulin (n = 2,744, 5.8%). Diabetic patients were older, suffered more frequently from comorbidities and presented more often with cardiogenic shock. The number of severely stenosed (≥70%) segments incrementally increased from nondiabetics to insulin-requiring diabetics. The location of lesions did not differ between patients with and without DM. The ratio stenosed/treated segments progressively rose among the four patient cohorts. The severity of DM negatively correlated with the extent of complete revascularization. After adjustment for confounding variables no significant differences in hospital mortality could be observed between patients without DM and diabetics treated with diet, but a significantly higher rate of death was seen in diabetic patients with oral medication and insulin therapy. Conclusions: Although CAD was more severe in patients with DM the percentage of treated segments with ≥70% stenosis was lower. Adjusted hospital mortality was increased among diabetics treated with oral medication or insulin, but not among those treated with diet. Copyright http://repub.eur.nl/res/pub/34610/ 2011-11-01T00:00:00Z Objectives: This study sought to evaluate the long-term clinical outcome of patients with an angiographically intermediate left anterior descending coronary artery (LAD) stenosis in whom the revascularization strategy was based on fractional flow reserve (FFR). Background: When revascularization is based mainly on angiographic guidance, a number of hemodynamically nonsignificant stenoses will be revascularized. Methods: In 730 patients with a 30% to 70% isolated stenosis in the proximal LAD and no significant valvular disease, FFR measurements were obtained to guide treatment strategy. When FFR was <0.80, the patients (n = 564) were treated medically (medical group); when FFR was <0.80, the patients (n = 166) underwent a revascularization procedure (revascularization group; 13% coronary artery bypass graft surgery and 87% percutaneous coronary intervention). A 100% long-term clinical follow-up (median follow-up: 40 months) was obtained. The 5-year survival of the medical group was compared with that of a reference population. For each patient, 4 controls were selected from an age- and sex-matched control population. Results: The 5-year survival estimate was 92.9% in the medical group versus 89.6% in the controls (p = 0.74). The mean diameter stenosis was significantly smaller in the medical than in the revascularization group (39 ± 14% vs. 54 ± 13%, p < 0.0001), but there was a large overlap between both groups. The 5-year event-free survival estimates (death, myocardial infarction, and target vessel revascularization) were 89.7% and 68.5%, respectively (p < 0.0001). Conclusions: Medical treatment of patients with a hemodynamically nonsignificant stenosis (FFR <0.80) in the proximal LAD is associated with an excellent long-term clinical outcome with survival at 5 years similar to an age- and sex-matched control population. http://repub.eur.nl/res/pub/33634/ 2011-09-01T00:00:00Z Background: The percentage of elderly treated with percutaneous coronary intervention (PCI) has been increasing year by year. Little is known about predictors of hospital mortality in elderly undergoing PCI for acute coronary syndromes (ACS) and stable angina. Methods: Between 2005 and 2008 a total of 47,407 consecutive patients undergoing PCI were prospectively enrolled into the PCI-Registry of the EHS Programme. For the present analysis patients were divided into four categories: ACS patients ≥ 75 (n = 4,943) and < 75 years (n = 19,446), and patients with stable angina ≥ 75 (n = 3,393) and < 75 years (n = 19,625). A multiple logistic regression analysis was conducted to detect independent predictors of mortality in patients ≥ 75 years undergoing PCI. In addition, differences in clinical characteristics, procedural details and in-hospital outcomes between the subgroups were evaluated. Results: Patients ≥ 75 years had more co-morbidities, and more severe coronary pathology. The use of guideline-recommended adjunctive therapy and procedural success was high in all groups. The incidence of in-hospital death was highest in ACS patients ≥ 75 years (5.2%) and < 75 years (1.7%), followed by patients with stable angina ≥ 75 (0.5%) and < 75 years (0.2%). Haemodynamic instability and acute ST-elevation myocardial infarction were the strongest determinants of hospital mortality among patients ≥ 75 years with ACS, whereas interventional complications were the most meaningful predictors of death in older patients undergoing elective PCI. Conclusions: Patients ≥ 75 years undergoing PCI face a relatively low risk of hospital death. However, complication rates were significantly higher compared to younger patients, strongly influenced by clinical, angiographic and interventional variables. http://repub.eur.nl/res/pub/26647/ 2011-07-18T00:00:00Z Objective: To assess the safety and efficacy of the Genous™ endothelial progenitor cell (EPC) capturing stent in conjunction with HmG-CoA-reductase inhibitors (statins) to stimulate EPC recruitment, in the treatment of patients with de novo coronary artery lesions. Methods and results: The HEALING IIB study was a multi-center, prospective trial, including 100 patients. The primary efficacy endpoint was late luminal loss by QCA at 6-month follow-up (FU). Although statin therapy increased relative EPC levels by 5.6-fold, the angiographic outcome at 6 month FU was not improved in patients with an overall in-stent late luminal loss of 0.76 ± 0.50 mm. The composite major adverse cardiac events (MACE) rate was 9.4%, whereas 6.3% clinically justified target lesion revascularizations (TLRs) were observed. 2 Patients died within the first 30 days after stent implantation due to angiographically verified in-stent thrombosis. At 12 month FU, MACE and TLR increased to 15.6% and 11.5% respectively and stabilized until 24 month FU. 18 Month angiographic FU showed a significant decrease in late luminal loss (0.67 ± 0.54, 11.8% reduction or 10% by matched serial analysis, P = 0.001). Conclusion: The HEALING IIB study suggests that statin therapy in combination with the EPC capture stent does not contribute to a reduction of in-stent restenosis formation for the treatment of de novo coronary artery disease. Although concomitant statin therapy was able to stimulate EPC recruitment, it did not improve the angiographic outcome of the bio-engineered EPC capture stent. Remarkably, angiographic late loss was significantly reduced between 6 and 18 months. http://repub.eur.nl/res/pub/33675/ 2011-06-01T00:00:00Z AimsThe applicability of currently available risk prediction models for patients undergoing percutaneous coronary interventions (PCIs) is limited. We aimed to develop a model for the prediction of in-hospital mortality after PCI that is based on contemporary and representative data from a European perspective. Methods and resultsOur analyses are based on the Euro Heart Survey of PCIs, which contains information on 46 064 consecutive patients who underwent PCI for different indications in 176 participating European centres during 200508. Patients were randomly divided into a training (n = 23 032) and a validation (n = 23 032) set with similar characteristics. In these sets, 339 (1.5) and 305 (1.3) patients died during hospitalization, respectively. On the basis of the training set, a logistic model was constructed that related 16 independent patient or lesion characteristics with mortality, including PCI indication, advanced age, haemodynamic instability, multivessel disease, and proximal LAD disease. In both the training and validation data sets, the model had a good performance in terms of discrimination (C-index 0.91 and 0.90, respectively) and calibration (HosmerLemeshow P-value 0.39 and 0.18, respectively). Conclusion In-hospital mortality in PCI patients was well predicted by a risk score that contains 16 factors. The score has strong applicability for European practices. http://repub.eur.nl/res/pub/33916/ 2011-05-31T00:00:00Z Objectives: The aim of this study was to investigate the impact of patient and lesion complexity on outcomes with newer-generation zotarolimus-eluting stents (ZES) and everolimus-eluting stents (EES). Background: Clinical and angiographic outcomes of newer-generation stents have not been described among complex patients. Methods: Patients enrolled in the RESOLUTE All Comers trial (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention) were stratified into "complex" and "simple." Results: Of 2,292 patients, 1,520 (66.3%) were complex and treated with ZES (n = 764) or EES (n = 756). Event rates were higher among complex patients, and results did not differ between ZES and EES, regardless of complexity. At 1 year, target lesion failure was 8.9% in ZES- and 9.7% in EES-treated complex patients (p = 0.66) and 6.8% in ZES- and 5.7% in EES-treated simple patients (p = 0.55). Rates of cardiac death (1.3% vs. 2.2%, p = 0.24), target-vessel myocardial infarction (4.3% vs. 4.4%, p = 0.90), and clinically indicated target lesion revascularization (4.4% vs. 4.0%, p = 0.80) were similar for both stent types among complex patients. Definite or probable stent thrombosis occurred in 20 (1.3%) complex patients with no difference between ZES (1.7%) and EES (0.9%, p = 0.26). Angiographic follow-up showed similar results for ZES and EES in terms of in-stent percentage diameter stenosis (22.2 ± 15.4% vs. 21.4 ± 15.8%, p = 0.67) and in-segment binary restenosis (6.6% vs. 8.0%, p = 0.82) in the complex group. Conclusions: In this all-comers randomized trial, major adverse cardiovascular events were more frequent among complex than simple patients. The newer-generation ZES and EES proved to be safe and effective, regardless of complexity, with similar clinical and angiographic outcomes for both stent types through 1 year. (RESOLUTE-III All Comers Trial: A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention; NCT00617084) http://repub.eur.nl/res/pub/25262/ 2011-05-19T00:00:00Z We explored the impact of patient demographics, anthropometric measurements, cardiovascular risk factors, and soluble biomarkers on necrotic core and atheroma size in patients with coronary disease. The IBIS-2 trial enrolled 330 patients. In the multivariate analysis, at baseline, creatinine had a positive, whereas baseline mean lumen diameter and myeloperoxidase had a negative, independent association with percentage of necrotic core (PNC); while age, glomerular filtration rate <60, HbA1c, previous PCI or CABG and baseline % diameter stenosis were positively, and acute coronary syndromes (ACS) were negatively associated with baseline percentage atheroma volume (PAV). The variables associated with a decrease in PNC from baseline were darapladib, ACS and a large content of NC at baseline, while variables associated with an increase in PNC were previous stroke and % diameter stenosis at baseline. Those variables associated with a decrease in PAV from baseline were waist circumference, statin use, CD40L and baseline PAV, while the only variable associated with an increase in PAV was baseline diastolic blood pressure. Treatment with darapladib was associated with a decrease in necrotic core, but was not associated with a decrease in percentage atheroma volume. On the contrary, statin use was only associated with a decrease in percentage atheroma volume. http://repub.eur.nl/res/pub/23288/ 2011-02-21T00:00:00Z Fractional flow reserve (FFR) is an index of the physiological significance of a coronary stenosis. Patients who have lesions with a FFR of >0.80, even optimally treated with medication, have however a MACE rate ranging from 8 to 21%. Coronary plaques at high risk of rupture and clinical events can be also identified by virtual histology intravascular ultrasound (IVUS-VH) as plaques with high amount of necrotic core (NC) abutting the lumen. Aim of this exploratory study was to investigate whether the geometry and composition of lesions with FFR ≤ 0.80 were different from their counterparts. Fifty-five consecutive patients in whom FFR was clinically indicated on a moderate angiographic lesion, received also an imaging investigation on the same lesion with IVUS-VH. Data on plaque geometry and composition was analyzed. Patients were subdivided in two groups according to the value of FFR (> or ≤0.80). Lesions with a FFR ≤ 0.80 (n = 17) showed a slightly larger plaque burden than those with FFR > 0.80 (n = 38) (54.6 ± 0.7% vs. 51.7 ± 0.7% P = 0.1). In addition, they tend to have less content of necrotic core than their counterparts (14.2 ± 8% vs. 19.2 ± 10.2%, P = 0.08). No difference was found in the distribution of NC-rich plaques (fibroatheroma and thin-capped fibroatheroma) between groups (82% in FFR ≤ 0.80 vs. 79% in FFR > 0.80, P = 0.5). Although FFR ≤ 0.80 lesions have larger plaque size, they do not differ in composition from the ones with FFR > 0.80. Further exploration in a large prospective study is needed to study whether the lesions with FFR > 0.80 that are NC rich are the ones associated with the presence of clinical events at follow-up. http://repub.eur.nl/res/pub/34687/ 2011-02-01T00:00:00Z Background-The age, creatinine, and ejection fraction (ACEF) score (age/left ventricular ejection fraction+1 if creatinine >2.0 mg/dL) has been established as an effective predictor of clinical outcomes in patients undergoing elective coronary artery bypass surgery; however, its utility in "all-comer" patients undergoing percutaneous coronary intervention is yet unexplored. Methods and Results-The ACEF score was calculated for 1208 of the 1707 patients enrolled in the LEADERS trial. Post hoc analysis was performed by stratifying clinical outcomes at the 1-year follow-up according to ACEF score tertiles: ACEFlow≤1.0225, 1.0225< ACEFmid≤1.277, and ACEFhigh>1.277. At 1-year follow-up, there was a significantly lower number of patients with major adverse cardiac event-free survival in the highest tertile of the ACEF score (ACEFlow=92.1%, ACEFmid=89.5%, and ACEFhigh=86.1%; P=0.0218). Cardiac death was less frequent in ACEFlowthan in ACEFmidand ACEFhigh(0.7% vs 2.2% vs 4.5%; hazard ratio=2.22, P=0.002) patients. Rates of myocardial infarction were significantly higher in patients with a high ACEF score (6.7% for ACEFhighvs 5.2% for ACEFmidand 2.5% for ACEFlow; hazard ratio=1.6, P=0.006). Clinically driven target-vessel revascularization also tended to be higher in the ACEFhighgroup, but the difference among the 3 groups did not reach statistical significance. The rate of composite definite, possible, and probable stent thrombosis was also higher in the ACEFhighgroup (ACEFlow=1.2%, ACEFmid=3.5%, and ACEFhigh=6.2%; hazard ratio=2.04, P=0.001). Conclusions-ACEF score may be a simple way to stratify risk of events in patients treated with percutaneous coronary intervention with respect to mortality and risk of myocardial infarction. http://repub.eur.nl/res/pub/20963/ 2010-07-20T00:00:00Z Objectives: We aimed to assess the predictive value of the SYNTAX score (SXscore) for major adverse cardiac events in the all-comers population of the LEADERS (Limus Eluted from A Durable versus ERodable Stent coating) trial. Background: The SXscore has been shown to be an effective predictor of clinical outcomes in patients with multivessel disease undergoing percutaneous coronary intervention. Methods: The SXscore was prospectively collected in 1,397 of the 1,707 patients enrolled in the LEADERS trial (patients after surgical revascularization were excluded). Post hoc analysis was performed by stratifying clinical outcomes at 1-year follow-up, according to 1 of 3 SXscore tertiles. Results: The 1,397 patients were divided into tertiles based on the SXscore in the following fashion: SXscore ≤8 (SXlow) (n = 464), SXscore >8 and ≤16 (SXmid) (n = 472), and SXscore >16 (SXhigh) (n = 461). At 1-year follow-up, there was a significantly lower number of patients with major cardiac event-free survival in the highest tertile of SXscore (SXlow = 92.2%, SXmid = 91.1%, and SXhigh = 84.6%; p < 0.001). Death occurred in 1.5% of SXlow patients, 2.1% of SXmid patients, and 5.6% of SXhigh patients (hazard ratio [HR]: 1.97, 95% confidence interval [CI]: 1.29 to 3.01; p = 0.002). The myocardial infarction rate tended to be higher in the SXhigh group. Target vessel revascularization was 11.3% in the SXhigh group compared with 6.3% and 7.8% in the SXlow and SXmid groups, respectively (HR: 1.38, 95% CI: 1.1 to 1.75; p = 0.006). Composite of cardiac death, myocardial infarction, and clinically indicated target vessel revascularization was 7.8%, 8.9%, and 15.4% in the SXlow, SXmid, and SXhigh groups, respectively (HR: 1.47, 95% CI: 1.19 to 1.81; p < 0.001). Conclusions: The SXscore, when applied to an all-comers patient population treated with drug-eluting stents, may allow prospective risk stratification of patients undergoing percutaneous coronary intervention. (LEADERS Trial Limus Eluted From A Durable Versus ERodable Stent Coating; NCT00389220) http://repub.eur.nl/res/pub/20630/ 2010-07-01T00:00:00Z BACKGROUND: New-generation coronary stents that release zotarolimus or everolimus have been shown to reduce the risk of restenosis. However, it is unclear whether there are differences in efficacy and safety between the two types of stents on the basis of prospectively adjudicated end points endorsed by the Food and Drug Administration. METHODS: In this multicenter, noninferiority trial with minimal exclusion criteria, we randomly assigned 2292 patients to undergo treatment with coronary stents releasing either zotarolimus or everolimus. Twenty percent of patients were randomly selected for repeat angiography at 13 months. The primary end point was target-lesion failure, defined as a composite of death from cardiac causes, any myocardial infarction (not clearly attributable to a nontarget vessel), or clinically indicated target-lesion revascularization within 12 months. The secondary angiographic end point was the extent of in-stent stenosis at 13 months. RESULTS: At least one off-label criterion for stent placement was present in 66% of patients. The zotarolimus-eluting stent was noninferior to the everolimus-eluting stent with respect to the primary end point, which occurred in 8.2% and 8.3% of patients, respectively (P<0.001 for noninferiority). There were no significant between-group differences in the rate of death from cardiac causes, any myocardial infarction, or revascularization. The rate of stent thrombosis was 2.3% in the zotarolimus-stent group and 1.5% in the everolimus-stent group (P = 0.17). The zotarolimus-eluting stent was also noninferior regarding the degree (±SD) of in-stent stenosis (21.65±14.42% for zotarolimus vs. 19.76±14.64% for everolimus, P = 0.04 for noninferiority). In-stent late lumen loss was 0.27±0.43 mm in the zotarolimus-stent group versus 0.19±0.40 mm in the everolimusstent group (P = 0.08). There were no significant between-group differences in the rate of adverse events. CONCLUSIONS: At 13 months, the new-generation zotarolimus-eluting stent was found to be noninferior to the everolimus-eluting stent in a population of patients who had minimal exclusion criteria. http://repub.eur.nl/res/pub/19851/ 2010-06-01T00:00:00Z Background: The most recent ESC guidelines for percutaneous coronary intervention (PCI) recommend the use of glycoprotein IIb/IIIa inhibitors (GPI) in high risk patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), particularly in diabetics. Little is known about the adherence to these guidelines within Europe. Methods and results: Between May 2005 and April 2008 a total of 47,407 consecutive patients undergoing PCI were prospectively enrolled into the PCI-Registry of the Euro Heart Survey Programme. In the present analysis we examined the use of GPI in 2,922 diabetics who underwent PCI for NSTE-ACS. In this high risk population only 22.2% received a GPI; 8.9% upstream and 13.4% during PCI. The strategy of the individual institution had a major impact on the usage of GPI. In the multiple regression analysis clinical instability and complex lesion characteristics were strong independent determinants for the use of GPI, whereas renal insufficiency was negatively associated with its use. After adjustment for confounding variables no significant differences in hospital mortality could be observed between the cohorts, but a significantly higher rate of non-fatal postprocedural myocardial infarction was observed among patients receiving GPI upstream. Conclusions: Despite the recommendation for its use in the current ESC guidelines, only a minority of the diabetics in Europe undergoing PCI for NSTE-ACS received a GPI. The use of GPI was mainly triggered by high-risk interventional scenarios. http://repub.eur.nl/res/pub/33147/ 2010-04-01T00:00:00Z Platelet response to clopidogrel shows inter-individual variability that is partially explained by genetic polymorphisms. This variability affects clinical outcome when clopidogrel is administered in patients with acute coronary syndrome (ACS). Catecholamines, released during ACS, contribute to platelet aggregation through platelet α2A- (α2A-AR) and β2-adrenergic receptor (β2-AR) stimulation. It was the objective of this study to assess the potential influence of α2A-AR and β2-AR gene polymorphisms on platelet reactivity after dual antiplatelet therapy with aspirin and clopidogrel in ACS. We screened 641 ACS patients for 6.3/6.7 kb α2A-AR polymorphism, and for Arg16Gly and Gln27Glu β2-AR polymorphism. After 600 mg clopidogrel, we assessed ADP 10 μmol-induced platelet aggregation (ADP-Ag) and vasoactive stimulated phosphoprotein (VASP). All single nucleotide polymorphisms were in Hardy-Weinberg equilibrium. A slight though negligible association was found between 6.3 kb allele of α2A- AR with platelet reactivity ADPAg induced (beta: -2.91 [-5.68;-0.14], p=0.04). A borderline not significant reduction in PRI VASP was observed in 6.3 kb α2A-AR carriers (beta: -3.81 [-0.09;7.72], p=0.06). No significant effect on platelet parameters was observed for the other tested polymorphisms. Common α2A- and β2-adrenergic receptor polymorphisms do not show any major impact on residual platelet reactivity in non-ST-elevation ACS when a dual antiplatelet therapy with 250 mg aspirin and 600 mg clopidogrel is administered. http://repub.eur.nl/res/pub/18221/ 2010-02-15T00:00:00Z The aim of this analysis was to assess the effect of body mass index (BMI) on 1-year outcomes in patients enrolled in a contemporary percutaneous coronary intervention trial comparing a sirolimus-eluting stent with a durable polymer to a biolimus-eluting stent with a biodegradable polymer. A total of 1,707 patients who underwent percutaneous coronary intervention were randomized to treatment with either biolimus-eluting stents (n = 857) or sirolimus-eluting stents (n = 850). Patients were assigned to 1 of 3 groups according to BMI: normal (<25 kg/m(2)), overweight (25 to 30 kg/m(2)), or obese (>30 kg/m(2)). At 1 year, the incidence of the composite of cardiac death, myocardial infarction, and clinically justified target vessel revascularization was assessed. In addition, rates of clinically justified target lesion revascularization and stent thrombosis were assessed. Cox proportional-hazards analysis, adjusted for clinical differences, was used to develop models for 1-year mortality. Forty-five percent of the patients (n = 770) were overweight, 26% (n = 434) were obese, and 29% (n = 497) had normal BMIs. At 1-year follow-up, the cumulative rate of cardiac death, myocardial infarction, and clinically justified target vessel revascularization was significantly higher in the obese group (8.7% in normal-weight, 11.3% in overweight, and 14.5% in obese patients, p = 0.01). BMI (hazard ratio 1.47, 95% confidence interval 1.02 to 2.14, p = 0.04) was an independent predictor of stent thrombosis. Stent type had no impact on the composite of cardiac death, myocardial infarction, and clinically justified target vessel revascularization at 1 year in the 3 BMI groups (hazard ratio 1.08, 95% confidence interval 0.63 to 1.83, p = 0.73). In conclusion, BMI was an independent predictor of major adverse cardiac events at 1-year clinical follow-up. The higher incidence of stent thrombosis in the obese group may suggest the need for a weight-adjusted dose of clopidogrel. http://repub.eur.nl/res/pub/27706/ 2010-01-01T00:00:00Z AimsCardiovascular risk factors such as elevated serum lipid levels are important in the development of coronary atherosclerosis. Radiofrequency (RF) analysis of intravascular ultrasound [IVUS, Virtual histology™ (VH)] offers a unique tool to study the composition of coronary atherosclerotic plaque in vivo. We used data from the multicentre VH registry to assess the association between cardiovascular risk factors and coronary plaque volume and composition.Methods and resultsBetween August 2004 and July 2006, 990 patients in 42 centres were enrolled in a prospective, multicentre, non-randomized global VH registry. Coronary artery imaging was performed by conventional IVUS and RF-IVUS. The four RF-IVUS plaque components [dense calcium (DC), necrotic core (NC), fibrous (F) tissue, and fibro fatty (FF)] were analysed in every recorded frame. The results were expressed as mean cross-sectional areas, absolute volume, and percentage of total plaque volume. Risk factor assessment included evaluation of family history of previous myocardial infarction (MI), past or current smoking, diabetes mellitus, hypertension, and the laboratory measurements. Patients with diabetes had an increased relative proportion of NC (6.47 ± 0.28 vs. 5.86 ± 0.14, P = 0.037) and DC (4.58 ± 0.27 vs. 3.90 ± 0.14, P = 0.017), and patients with hypertension had an increased relative proportion of FF, DC (4.35 ± 0.16 vs. 3.57 ± 0.17, P = 0.02) and NC (6.24 ± 0.17 vs. 5.60 ± 0.19, P = 0.01). Compared with patients with LDL-C <100 mg/dL, patients with LDL-C >160 mg/dL had higher plaque volume (342.1 ± 26.2 vs. 318.6 ± 10.7 mm3). Linear regression analysis showed a correlation between the level of HDL-C and F (r =-0.149, P < 0.01), FF (r =-0.106, P < 0.01), and NC (r =-0.90, P < 0.05). The level of LDL correlated with F (r = 0.110, P < 0.01). Patients with prior MI have an increased percentage of F (30.03 ± 0.59 vs. 28.20 ± 0.37, P = 0.009). Smoking had no relevant effect on plaque composition. Treatment with acetylsalicylacid and statins reduced FF with altering plaque volume.ConclusionRadiofrequency-IVUS detects marked differences in coronary plaque composition related to the risk factor profile with particular focus on lipid levels. Greater amounts of NC were associated with diabetes, hypertension, MI, and low HDL-C. The effects of treatment of changes related to plaque composition are underway. http://repub.eur.nl/res/pub/24249/ 2009-12-01T00:00:00Z Drug-eluting stents (DES) reduce restenosis rates compared to bare-metal stents. Most trials using DES enrolled selected patient and lesion subtypes, and primary endpoint focused on angiographic metrics or relatively short-term outcomes. When DES are used in broader types of lesions and patients, important differences may emerge in long-term outcomes between stent types, particularly the incidence of late stent thrombosis. PROTECT is a randomized, open-label trial comparing the long-term safety of the zotarolimus-eluting stent and the sirolimus-eluting stent. The trial has enrolled 8,800 patients representative of those seen in routine clinical practice, undergoing elective, unplanned, or emergency procedures in native coronary arteries in 196 centers in 36 countries. Indications for the procedure and selection of target vessel and lesion characteristics were at the operator's discretion. Procedures could be staged, but no more than 4 target lesions could be treated per patient. Duration of dual antiplatelet therapy was prespecified to achieve similar lengths of treatment in both study arms. The shortest predefined duration was 3 months, as per the manufacturer's instructions. The primary outcome measure is the composite rate of definite and probable stent thrombosis at 3 years, centrally adjudicated using Academic Research Consortium definitions. The main secondary end points are 3-year all-cause mortality, cardiac death, large nonfatal myocardial infarction, and all myocardial infarctions. This large, international, randomized, controlled trial will provide important information on comparative rates of stent thrombosis between 2 different DES systems and safety as assessed by patient-relevant long-term clinical outcomes. http://repub.eur.nl/res/pub/24413/ 2009-09-01T00:00:00Z Objectives: We assessed the impact of vessel size on outcomes of stenting with biolimus-eluting degradable polymer stent (BES) and sirolimus-eluting permanent polymer stent (SES) within a randomized multicenter trial (LEADERS). Background: Stenting of small vessels might be associated with higher rates of adverse events. Methods: "All-comer" patients (n = 1,707) were randomized to BES and SES. Post-hoc-stratified analysis of angiographic and clinical outcomes at 9 months and 1 year, respectively, was performed for vessels with reference diameter ≤2.75 mm versus >2.75 mm. Results: Of 1,707 patients, 429 patients in the BES group with 576 lesions and 434 patients in the SES group with 557 lesions had only small vessels treated (50.6% of the patient cohort). In patients with small vessels there was no significant difference in overall major adverse cardiac events (MACE) rate (12.1% vs. 11.8%; p = 0.89) or target lesion revascularization (TLR) rate (9.6% vs. 7.4%; p = 0.26) between BES and SES. The MACE and TLR rates in the small-vessel patient population were higher than in the large-vessel population. The TLR rate was 9.6% versus 2.6%, and MACE rate was 12.1% versus 7.1% for small versus large vessels in the BES arm (TLR: hazard ratio [HR] = 3.724, p = 0.0013; MACE: HR = 1.720, p = 0.0412). In the SES arm, TLR was 7.4% versus 5.1%, and MACE was 11.8% versus 10.3% in small versus large vessels (TLR: HR = 1.435, p = 0.2594; MACE: HR = 1.149, p = 0.5546). Conclusions: Prevalence of small vessel disease is high in an "all-comer" population with higher TLR and MACE rates. The BES and SES seem equivalent in treatment outcomes of small vessels in this "all-comer" patient population. http://repub.eur.nl/res/pub/25279/ 2009-06-01T00:00:00Z Background-The newly developed Nobori coronary stent coated with a bioresorbable polymer, polylactic acid, and the antiproliferative agent Biolimus A9 has the potential to reduce restenosis by suppressing neointima formation. Methods and Results-We conducted a randomized (2:1), controlled trial comparing the Biolimus A9- eluting stent Nobori and the paclitaxel-eluting stent Taxus Liberté, in 243 patients (153 Nobori and 90 Taxus) at 29 centers in Europe, Asia, and Australia. Patients with previously untreated lesions in up to 2 native coronary arteries were considered for enrollment. The primary end point was in-stent late loss at 9 months, whereas secondary end points included other quantitative coronary angiography parameters, such as in-segment late loss and the rate of restenosis as well as key intravascular ultrasound parameters. Clinical secondary end points were stent thrombosis and composite of major adverse cardiac events comprising death, myocardial infarction, and target vessel revascularization. At 9 months, the in-stent late loss was significantly lower in the Nobori group compared with the Taxus group (0.11±0.30 mm versus 0.32±0.50 mm) reaching both the primary hypothesis of noninferiority of Nobori stent versus Taxus Liberté stent (P=0.001) and the secondary hypothesis of superiority (P<0.001). This finding was confirmed by a significant reduction in binary restenosis from 6.2% in Taxus to 0.7% in Nobori (P=0.02) and neointimal volume obstruction, detected by intravascular ultrasound, from 5.5±7.2% in Taxus to 1.8±5.2% in Nobori (P=0.01). The major adverse cardiac events rate was 4.6% in the Nobori and 5.6% in the Taxus cohort of patients. The stent thrombosis rate was 0% in the Nobori arm and 4.4% in the Taxus arm. Conclusions-The NOBORI 1 clinical trial confirmed its primary hypothesis-noninferiority of the Nobori Biolimus A9-eluting stent versus the Taxus Liberté stent in reducing neointimal proliferation. Both stents showed a low major adverse cardiac events rate in the studied population. http://repub.eur.nl/res/pub/24400/ 2009-02-17T00:00:00Z Objectives: This study was designed to determine whether multislice computed tomography (MSCT) coronary angiography has incremental prognostic value over single-photon emission computed tomography myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD). Background: Although MSCT is used for the detection of CAD in addition to MPI, its incremental prognostic value is unclear. Methods: In 541 patients (59% male, age 59 ± 11 years) referred for further cardiac evaluation, both MSCT and MPI were performed. The following events were recorded: all-cause death, nonfatal infarction, and unstable angina requiring revascularization. Results: In the 517 (96%) patients with an interpretable MSCT, significant CAD (MSCT ≥50% stenosis) was detected in 158 (31%) patients, and abnormal perfusion (summed stress score [SSS]: ≥4) was observed in 168 (33%) patients. During follow-up (median 672 days; 25th, 75th percentile: 420, 896), an event occurred in 23 (5.2%) patients. After correction for baseline characteristics in a multivariate model, MSCT emerged as an independent predictor of events with an incremental prognostic value to MPI. The annualized hard event rate (all-cause mortality and nonfatal infarction) in patients with none or mild CAD (MSCT <50% stenosis) was 1.8% versus 4.8% in patients with significant CAD (MSCT ≥50% stenosis). A normal MPI (SSS <4) and abnormal MPI (SSS ≥4) were associated with an annualized hard event rate of 1.1% and 3.8%, respectively. Both MSCT and MPI were synergistic, and combined use resulted in significantly improved prediction (log-rank test p value <0.005). Conclusions: MSCT is an independent predictor of events and provides incremental prognostic value to MPI. Combined anatomical and functional assessment may allow improved risk stratification. http://repub.eur.nl/res/pub/27090/ 2009-01-01T00:00:00Z http://repub.eur.nl/res/pub/14686/ 2008-10-01T00:00:00Z Aims: Atherosclerotic plaque characteristics play an important role in the development of coronary events. We investigated coronary plaque characteristics on multi-slice computed tomography (MSCT) and virtual histology intravascular ultrasound (VH IVUS) in patients with acute coronary syndromes (ACS) and stable coronary artery disease (CAD). Methods and results: Fifty patients (25 with ACS, 25 with stable CAD) underwent 64-slice MSCT followed by VH IVUS in 48 (96%) patients. In ACS patients, 32% of plaques were non-calcified on MSCT and 59% were mixed [corresponding odds ratio (95% confidence intervals): 3.9 (1.6-9.5), P = 0.003 and 3.4 (1.6-6.9), P = 0.001, respectively]. In patients with stable CAD, completely calcified lesions were more prevalent (61%). On VH IVUS, the percentage of necrotic core was higher in the plaques of ACS patients (11.16 ± 6.07 vs. 9.08 ± 4.62% in stable CAD, P = 0.02). In addition, thin cap fibroatheroma was more prevalent in ACS patients (32 vs. 3% in patients with stable CAD, P < 0.001) and was most frequently observed in mixed plaques on MSCT. Plaque composition both on MSCT and VH IVUS was identical between culprit and non-culprit vessels of ACS patients. Conclusion: On MSCT, differences in plaque characterization were demonstrated between patients with ACS and stable CAD. Plaques of ACS patients showed features of vulnerability to rupture on VH IVUS. Potentially, MSCT may be useful for non-invasive identification of atherosclerotic plaque patterns associated with higher risk. http://repub.eur.nl/res/pub/28817/ 2008-09-09T00:00:00Z Background - Lipoprotein-associated phospholipase A2 (Lp-PLA2) is expressed abundantly in the necrotic core of coronary lesions, and products of its enzymatic activity may contribute to inflammation and cell death, rendering plaque vulnerable to rupture. Methods and Results - This study compared the effects of 12 months of treatment with darapladib (an oral Lp-PLA2 inhibitor, 160 mg daily) or placebo on coronary atheroma deformability (intravascular ultrasound palpography) and plasma high-sensitivity C-reactive protein in 330 patients with angiographically documented coronary disease. Secondary end points included changes in necrotic core size (intravascular ultrasound radiofrequency), atheroma size (intravascular ultrasound gray scale), and blood biomarkers. Background therapy was comparable between groups, with no difference in low-density lipoprotein cholesterol at 12 months (placebo, 88±34 mg/dL; darapladib, 84±31 mg/dL; P=0.37). In contrast, Lp-PLA2 activity was inhibited by 59% with darapladib (P<0.001 versus placebo). After 12 months, there were no significant differences between groups in plaque deformability (P=0.22) or plasma high-sensitivity C-reactive protein (P=0.35). In the placebo-treated group, however, necrotic core volume increased significantly (4.5±17.9 mm; P=0.009), whereas darapladib halted this increase (-0.5±13.9 mm; P=0.71), resulting in a significant treatment difference of -5.2 mm (P=0.012). These intraplaque compositional changes occurred without a significant treatment difference in total atheroma volume (P=0.95). Conclusions - Despite adherence to a high level of standard-of-care treatment, the necrotic core continued to expand among patients receiving placebo. In contrast, Lp-PLA2 inhibition with darapladib prevented necrotic core expansion, a key determinant of plaque vulnerability. These findings suggest that Lp-PLA2 inhibition may represent a novel therapeutic approach. http://repub.eur.nl/res/pub/14726/ 2008-09-01T00:00:00Z Background: A novel stent platform eluting biolimus, a sirolimus analogue, from a biodegradable polymer showed promising results in preliminary studies. We compared the safety and efficacy of a biolimus-eluting stent (with biodegradable polymer) with a sirolimus-eluting stent (with durable polymer). Methods: We undertook a multicentre, assessor-blind, non-inferiority study in ten European centres. 1707 patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes were centrally randomised by a computer-generated allocation sequence to treatment with either biolimus-eluting (n=857) or sirolimus-eluting (n=850) stents. The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation within 9 months. Analysis was by intention to treat. 427 patients were randomly allocated to angiographic follow-up, with in-stent percentage diameter stenosis as principal outcome measure at 9 months. The trial is registered with ClinicalTrials.gov, number NCT00389220. Findings: We analysed all randomised patients. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents for the primary endpoint at 9 months (79 [9%] patients vs 89 [11%], rate ratio 0·88 [95% CI 0·64-1·19], p for non-inferiority=0·003, p for superiority=0·39). Frequency of cardiac death (14 [1·6%] vs 21 [2·5%], p for superiority=0·22), myocardial infarction (49 [5·7%] vs 39 [4·6%], p=0·30), and clinically-indicated target vessel revascularisation (38 [4·4%] vs 47 [5·5%], p=0·29) were similar for both stent types. 168 (79%) patients in the biolimus-eluting group and 167 (78%) in the sirolimus-eluting group had data for angiographic follow-up available. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents in in-stent percentage diameter stenosis (20·9% vs 23·3%, difference -2·2% [95% CI -6·0 to 1·6], p for non-inferiority=0·001, p for superiority=0·26). Interpretation: Our results suggest that a stent eluting biolimus from a biodegradable polymer represents a safe and effective alternative to a stent eluting sirolimus from a durable polymer in patients with chronic stable coronary artery disease or acute coronary syndromes. Funding: Biosensors Europe SA, Switzerland. http://repub.eur.nl/res/pub/29140/ 2008-05-01T00:00:00Z BACKGROUND: Noninvasive assessment of coronary atherosclerotic plaque may be useful for risk stratification and treatment of atherosclerosis. MATERIALS AND METHODS: We studied 47 patients to investigate the accuracy of coronary plaque volume measurement acquired with 64-slice multislice computed tomography (MSCT), using newly developed quantification software, when compared with quantitative intracoronary ultrasound (QCU). Quantitative MSCT coronary angiography (QMSCT-CA) was performed to determine plaque volume for a matched region of interest (regional plaque burden) and in significant plaque defined as a plaque with ≥50% area obstruction in QCU, and compared with QCU. Dataset with image blurring and heavy calcification were excluded from analysis. RESULTS: In 100 comparable regions of interest, regional plaque burden was highly correlated (coefficient r = 0.96; P < 0.001) between QCU and QMSCT-CA, but QMSCT-CA overestimated the plaque burden by a mean difference of 7 ± 33 mm (P = 0.03). In 76 significant plaques detected within the regions of interest, plaque volume determined by QMSCT-CA was highly correlated (r = 0.98; P < 0.001) with a slight underestimation of 2 ± 17 mm (P = not significant) when compared with QCU. Calcified and mixed plaque volume was slightly overestimated by 4 ± 19 mm (P = ns) and noncalcified plaque volume was significantly underestimated by 9 ± 11 mm (P < 0.001) with QMSCT-CA. Overall, the limits of agreement for plaque burden/volume measurement between QCU and QMSCT-CA were relatively large. Reproducibility for the measurements of regional plaque burden with QMSCT-CA was good, with a mean intraobserver and interobserver variability of 0% ± 16% and 4% ± 24%, respectively. CONCLUSIONS: Quantification of coronary plaque within selected proximal or middle coronary segments without image blurring and heavy calcification with 64-slice CT was moderately accurate with respect to intravascular ultrasound and demonstrated good reproducibility. Further improvement in CT resolution is required for more reliable measurement of coronary plaques using quantification software. http://repub.eur.nl/res/pub/35290/ 2007-08-01T00:00:00Z Purpose: To review the literature on the diagnostic performance of multidetector computed tomographic (CT) angiography for assessment of symptomatic coronary artery disease, with conventional coronary angiography as the reference standard. Materials and A PubMed and manual search of the literature published Methods: between January 1998 and May 2006 on use of multidetector CT angiography compared with coronary angiography in patients with symptomatic coronary artery disease was performed. Summary estimates of diagnostic odds ratio, sensitivity, and specificity were calculated. Random-effects models were used to compare the diagnostic performance of four-, 16-, and 64-detector CT angiographic units, and the proportion of nonassessable coronary arterial segments was evaluated. Results: Fifty-four studies were included in the meta-analysis: 22 studies with four-detector CT angiography, 26 with 16-detector CT angiography, and six with 64-detector CT angiography. The pooled sensitivity and specificity for detecting a greater than 50% stenosis per segment were 0.93 (95% confidence interval [CI]: 0.88, 0.97) and 0.96 (95% CI: 0.96, 0.97) for 64-detector CT angiography, 0.83 (95% CI: 0.76, 0.90) and 0.96 (95% CI: 0.95, 0.97) for 16-detector CT angiography, and 0.84 (95% CI: 0.81, 0.88) and 0.93 (95% CI: 0.91, 0.95) for four-detector CT angiography, respectively. Results of regression analysis indicated that the diagnostic performance significantly improved with the newer generations of multidetector CT scanners (64- and 16-detector vs four-detector units), adjusted for exclusion of nonassessable segments, and contrast agent concentration used (P < .05). Simultaneously, the nonassessable proportion of segments significantly decreased with the newer generations of multidetector CT scanners, adjusted for heart rate, prevalence of significant disease, and mean age. Conclusion: With the newer generations of multidetector CT scanners, the diagnostic performance for the assessment of coronary artery disease has significantly improved, and the proportion of nonassessable segments has decreased. http://repub.eur.nl/res/pub/36204/ 2007-05-29T00:00:00Z Objectives: The purpose of this study was to investigate the appropriateness of stenting a functionally nonsignificant stenosis. Background: Percutaneous coronary intervention (PCI) of an intermediate stenosis without evidence of ischemia is often performed, but its benefit is unproven. Coronary pressure-derived fractional flow reserve (FFR) is an invasive index used to identify a stenosis responsible for reversible ischemia. Methods: In 325 patients scheduled for PCI of an intermediate stenosis, FFR was measured just before the planned intervention. If FFR was ≥0.75, patients were randomly assigned to deferral (Defer group; n = 91) or performance (Perform group; n = 90) of PCI. If FFR was <0.75, PCI was performed as planned (Reference group; n = 144). Clinical follow-up was 5 years. Results: There were no differences in baseline clinical characteristics between the 3 groups. Complete follow-up was obtained in 98% of the patients. Event-free survival was not different between the Defer and Perform groups (80% and 73%, respectively; p = 0.52), but was significantly worse in the Reference group (63%; p = 0.03). The composite rate of cardiac death and acute myocardial infarction in the Defer, Perform, and Reference groups was 3.3%, 7.9%, and 15.7%, respectively (p = 0.21 for Defer vs. Perform group; p = 0.003 for the Reference vs. both other groups). The percentage of patients free from chest pain at follow-up was not different between the Defer and Perform groups. Conclusions: Five-year outcome after deferral of PCI of an intermediate coronary stenosis based on FFR ≥0.75 is excellent. The risk of cardiac death or myocardial infarction related to this stenosis is <1% per year and not decreased by stenting. http://repub.eur.nl/res/pub/36812/ 2007-03-01T00:00:00Z Objective: Self-perceived health status may be helpful in identifying patients at high risk for adverse outcomes. The Euro Heart Survey on Coronary Revascularization (EHS-CR) provided an opportunity to explore whether impaired health status was a predictor of 1-year mortality in patients with coronary artery disease (CAD) undergoing angiographic procedures. Methods: Data from the EHS-CR that included 5619 patients from 31 member countries of the European Society of Cardiology were used. Inclusion criteria for the current study were completion of a self-report measure of health status, the EuroQol Questionnaire (EQ-5D) at discharge and information on 1-year follow-up, resulting in a study population of 3786 patients. Results: The 1-year mortality was 3.2% (n = 120). Survivors reported fewer problems on the five dimensions of the EQ-5D as compared with non-survivors. A broad range of potential confounders were adjusted for, which reached a p<0.10 in the unadjusted analyses. In the adjusted analyses, problems with self-care (OR 3.45; 95% CI 2.14 to 5.59) and a low rating (≤ 60) on health status (OR 2.41; 95% CI 1.47 to 3.94) were the most powerful independent predictors of mortality, among the 22 clinical variables included in the analysis. Furthermore, patients who reported no problems on all five dimensions had significantly lower 1-year mortality rates (OR 0.47; 95% CI 0.28 to 0.81). Conclusions: This analysis shows that impaired health status is associated with a 2-3-fold increased risk of all-cause mortality in patients with CAD, independent of other conventional risk factors. These results highlight the importance of including patients' subjective experience of their own health status in the evaluation strategy to optimise risk stratification and management in clinical practice. http://repub.eur.nl/res/pub/13747/ 2005-06-01T00:00:00Z AIMS: The purpose of the Euro Heart Survey Programme of the European Society of Cardiology is to evaluate to which extent clinical practice endorses existing guidelines as well as to identify differences in population profiles, patient management, and outcome across Europe. The current survey focuses on the invasive diagnosis and treatment of patients with established coronary artery disease (CAD). METHODS AND RESULTS: Between November 2001 and March 2002, 7769 consecutive patients undergoing invasive evaluation at 130 hospitals (31 countries) were screened for the presence of one or more coronary stenosis >50% in diameter. Patient demographics and comorbidity, clinical presentation, invasive parameters, treatment options, and procedural techniques were prospectively entered in an electronic database (550 variables+29 per diseased coronary segment). Major adverse cardiac events (MACE) were evaluated at 30 days and 1 year. Out of 5619 patients with angiographically proven coronary stenosis (72% of screened population), 53% presented with stable angina while ST elevation myocardial infarction (STEMI) was the indication for coronary angiography in 16% and non-ST segment elevation myocardial infarction or unstable angina in 30%. Only medical therapy was continued in 21%, whereas mechanical revascularization was performed in the remainder [percutaneous coronary intervention (PCI) in 58% and coronary artery bypass grafting (CABG) in 21%]. Patients referred for PCI were younger, were more active, had a lower risk profile, and had less comorbid conditions. CABG was performed mostly in patients with left main lesions (21%), two- (25%), or three-vessel disease (67%) with 4.1 diseased segments, on average. Single-vessel PCI was performed in 82% of patients with either single- (45%), two- (33%), or three-vessel disease (21%). Stents were used in 75% of attempted lesions, with a large variation between sites. Direct PCI for STEMI was performed in 410 cases, representing 7% of the entire workload in the participating catheterization laboratories. Time delay was within 90 min in 76% of direct PCI cases. In keeping with the recommendations of practice guidelines, the survey identified under-use of adjunctive medication (GP IIb/IIIa receptor blockers, statins, and angiotensin-converting enzyme-inhibitors). Mortality rates at 30 days and 1 year were low in all subgroups. MACE primarily consisted of repeat PCI (12%). CONCLUSION: The current Euro Heart Survey on coronary revascularization was performed in the era of bare metal stenting and provides a global European picture of the invasive approach to patients with CAD. These data will serve as a benchmark for the future evaluation of the impact of drug-eluting stents on the practice of interventional cardiology and bypass surgery. http://repub.eur.nl/res/pub/13703/ 2005-03-01T00:00:00Z BACKGROUND: The use of sirolimus-eluting coronary stents has been associated with a nearly complete elimination of restenosis at 6 months and with a very low 1-year incidence of major adverse cardiac events (MACE). This analysis examined whether these beneficial effects persist over the longer term. METHODS AND RESULTS: This multicenter trial randomly assigned 238 patients to revascularization of single, de novo, native coronary artery lesions with sirolimus-eluting versus conventional bare-metal stents. Survival free from target lesion revascularization (TLR), target vessel failure (TVF), and MACE up to 3 years of follow-up was compared between the 2 treatment groups. Complete data sets were available in 94.2% of patients treated with sirolimus-eluting stents and in 94.1% of patients randomized to the control group. The cumulative 1-, 2-, and 3-year event-free survival rates were 99.2%, 96.5%, and 93.7% for TLR and 95.8%, 92.3%, and 87.9% for TVF, respectively, in the sirolimus-eluting stent group, versus 75.9%, 75.9%, and 75.0% for TLR and 71.2%, 69.4%, and 67.3% for TVF in the control group (P<0.001 for both comparisons at 3 years). Rates of MACE at 3 years were 15.8% in patients randomly assigned to sirolimus-eluting stents versus 33.1% in patients assigned to bare-metal stents (P=0.002). One patient treated with a sirolimus-eluting stent died of a cardiac cause between 12 and 36 months. CONCLUSIONS: Treatment of de novo coronary stenosis with sirolimus-eluting stents was associated with a sustained clinical benefit and very low rates of TLR and of other MACE up to 3 years after device implantation. http://repub.eur.nl/res/pub/4648/ 2004-08-04T00:00:00Z Abstract OBJECTIVES: We sought to assess the efficacy of vascular brachytherapy (VBT) combined with stenting for the primary prevention of restenosis. BACKGROUND: Intravascular brachytherapy after stent implantation for de novo lesions has been abandoned for the present. We revisited this procedure by optimizing all procedural steps-the use of glycoprotein IIb/IIa blockers, direct stenting, adequate radiation coverage, avoidance of edge damage, source centering, intravascular ultrasound-guided dosimetry, and continuation of a dual anti-platelet regimen for one year. METHODS: The Beta-Radiation Investigation with Direct stenting and Galileo in Europe (BRIDGE) study is a multicenter, randomized controlled trial evaluating the long-term efficacy of VBT with P-32 (20 Gy at 1 mm in the coronary wall) after direct stenting. The primary end point was angiographic intra-stent late loss; secondary end points were six months binary restenosis and neo-intimal hyperplasia. Patients (n = 112) with de novo lesions (2.5 to 4.0 mm in diameter up to 15 mm long) were randomized to either VBT or no-VBT. RESULTS: At six months, intra-stent loss was 0.43 and 0.84 mm (p < 0.001) in the irradiated and control groups, respectively. Intra-stent neo-intimal volume was reduced from 36 mm3 to 10 mm3. However, in the irradiated group there were six late occlusions as well as eight restenoses outside the stented and peri-stented area at the fall-off dose edges of the irradiated area. Accordingly, the target vessel revascularization and major adverse cardiac and cerebrovascular events rates at one year in the VBT group (20.4% and 25.9%, respectively) were higher than in the control group (12.1% and 17.2%, respectively). CONCLUSIONS: Despite the optimization of pre-, peri-, and post-procedural factors and despite the relative efficacy of the brachytherapy for the prevention of the intra-stent neo-intimal hyperplasia, the clinical outcome of the irradiated group was less favorable than that of the control group. http://repub.eur.nl/res/pub/4700/ 2003-12-01T00:00:00Z Abstract The aim of this prospective, multicenter, single arm study was to assess the safety and feasibility of EXPRESS Coronary Stent implantation in native coronary arteries without balloon predilatation. Forty-two patients with de novo or restenotic lesions were enrolled, of which 38 were eligible for analysis. The coronary lesions were predominantly complex, occurring in arteries with a mean reference diameter of 2.80 +/- 0.49 mm. Technical and procedural success were achieved in 89.5% and 84% of the cases respectively. The mean minimal lumen diameter increased from 1.08 +/- 0.26 mm to 2.55 +/- 0.44 mm and diameter stenosis decreased from 61 +/- 7% to 13 +/- 8%. The primary endpoint of major adverse cardiac events at 30 days was 2.6% and was limited to only one event (target vessel revascularization, nontarget lesion). No other MACE were observed during the three-month follow-up period. Based on the findings of this study, direct stenting with the EXPRESS Stent appears feasible and is well tolerated. http://repub.eur.nl/res/pub/10115/ 2003-03-01T00:00:00Z AIMS: To investigate the clinical and angiographic outcome of patients with mild coronary lesions treated with balloon angioplasty or coronary stenting (coronary plaque sealing, i.e. dilatation of angiographically non-significant lesions) compared to moderate and severe stenoses. METHODS AND RESULTS: Patients with chronic stable angina and a single de novo lesion in a native coronary vessel scheduled to undergo percutaneous coronary intervention (PCI) were selected from 14 different studies. Off-line analysis of angiographic outcomes was assessed in all patients using identical and standardised methods of data acquisition, analysis and definitions. Clinical endpoints were adjudicated by independent clinical events committees. All quantitative coronary angiographic (QCA) analyses were performed in the same core laboratory. Stenosis severity prior to PCI was categorised into three groups: <50% diameter stenosis (DS), 50-99%DS and >99%DS pre. A total of 3812 patients were included in this study; 1484 patients (39%) were successfully treated with balloon angioplasty (BA) only and stented angioplasty was performed in 2328 patients (61%).One-year mortality and rate of non-fatal myocardial infarction (MI) (Kaplan-Meier) did not differ between BA and stented angioplasty for any of the stenosis severity categories. Following BA, the combined event rate (death and non-fatal MI) was 4.8, 4.6 and 0% in the <50, 50-99 and >99%DS categories, respectively. Following stented angioplasty, the combined event rate was 3.1, 4.4 and 4.8% in the same categories. The need for repeat revascularisation corrected for stenosis severity in the Cox proportional-hazards regression model was reduced by 20% after stented angioplasty (hazard ratio (HR) 0.80, 95%CI 0.69-0.93). CONCLUSION: The concept of plaque sealing is appealing from the theoretical point of view. However, with current technology, plaque sealing cannot prevent death and future non-fatal MIs in the long-term because 1-year event rates after PCI of non-significant stenoses remain unacceptably elevated when compared with the estimated 1-year probability of a non-fatal MI in lesions with a <50%DS. Moreover, major adverse cardiac events at 1-year after PCI are not directly related to the degree of pre-procedural stenosis severity. http://repub.eur.nl/res/pub/9995/ 2002-10-08T00:00:00Z BACKGROUND: Restenosis remains the major limitation of coronary catheter-based intervention. In small vessels, the amount of neointimal tissue is disproportionately greater than the vessel caliber, resulting in higher restenosis rates. In the Randomized Study With the Sirolimus-Eluting Bx Velocity Balloon-Expandable Stent (RAVEL) trial, approximately 40% of the vessels were small (<2.5 mm). The present study evaluates the relationship between angiographic outcome and vessel diameter for sirolimus-eluting stents. METHODS AND RESULTS: Patients were randomized to receive either an 18-mm bare metal Bx VELOCITY (BS group, n=118), or a sirolimus-eluting Bx VELOCITY stent (SES group, n=120). Subgroups were stratified into tertiles according to their reference diameter (RD; stratum I, RD <2.36 mm; stratum II, RD 2.36 mm to 2.84 mm; stratum III, RD >2.84 mm). At 6-month follow-up, the restenosis rate in the SES group was 0% in all strata (versus 35%, 26%, and 20%, respectively, in the BS group). In-stent late loss was 0.01+/-0.25 versus 0.80+/-0.43 mm in stratum I, 0.01+/-0.38 versus 0.88+/-0.57 mm in stratum II, and -0.06+/-0.35 versus 0.74+/-0.57 mm in stratum III (SES versus BS). In SES, the minimal lumen diameter (MLD) remained unchanged (Delta -0.72 to 0.72 mm) in 97% of the lesions and increased (=late gain, DeltaMLD <-0.72 mm) in 3% of the lesions. Multivariate predictors for late loss were treatment allocation (P<0.001) and postprocedural MLD (P= 0.008). CONCLUSIONS: Sirolimus-eluting stents prevent neointimal proliferation and late lumen loss irrespective of the vessel diameter. The classic inverse relationship between vessel diameter and restenosis rate was seen in the bare stent group but not in the sirolimus-eluting stent group. http://repub.eur.nl/res/pub/4774/ 2002-08-13T00:00:00Z Background— The goal of this intravascular ultrasound investigation was to provide a more detailed morphological analysis of the local biological effects of the implantation of a sirolimus-eluting stent compared with an uncoated stent. Methods and Results— In the RAVEL trial, 238 patients with single de novo lesions were randomized to receive either an 18-mm sirolimus-eluting stent (Bx VELOCITY stent, Cordis) or an uncoated stent (Bx VELOCITY stent). In a subset of 95 patients (sirolimus-eluting stent=48, uncoated stent=47), motorized intravascular ultrasound pullback (0.5 mm/s) was performed at a 6-month follow-up. Stent volumes, total vessel volumes, and plaque-behind-stent volumes were comparable. However, the difference in neointimal hyperplasia (2±5 versus 37±28 mm3) and percent of volume obstruction (1±3% versus 29±20%) at 6 months between the 2 groups was highly significant (P<0.001), emphasizing the nearly complete abolition of the proliferative process inside the drug-eluting stent. Analysis of the proximal and distal edge volumes showed no significant difference between the 2 groups in external elastic membrane or lumen and plaque volume at the proximal and distal edges. There was also no evidence of intrastent thrombosis or persisting dissection at the stent edges. Although there was a higher incidence of incomplete stent apposition in the sirolimus group compared with the uncoated stent group (P<0.05), it was not associated with any adverse clinical events at 1 year. Conclusions— Sirolimus-eluting stents are effective in preventing neointimal hyperplasia without creating edge effect and without affecting the plaque burden behind the struts. http://repub.eur.nl/res/pub/4797/ 2002-02-20T00:00:00Z OBJECTIVES: We sought to assess the relationship between completeness of revascularization and adverse events at one year in the ARTS (Arterial Revascularization Therapies Study) trial. BACKGROUND: There is uncertainty to what extent degree of completeness of revascularization, using up-to-date techniques, influences medium-term outcome. METHODS: After consensus between surgeon and cardiologist regarding the potential for equivalence in the completeness of revascularization, 1,205 patients with multivessel disease were randomly assigned to either bypass surgery or stent implantation. All baseline and procedural angiograms and surgical case-record forms were centrally assessed for completeness of revascularization. RESULTS: Of 1,205 patients randomized, 1,172 underwent the assigned treatment. Complete data for review were available in 1,143 patients (97.5%). Complete revascularization was achieved in 84.1% of the surgically treated patients and 70.5% of the angioplasty patients (p < 0.001). After one year, the stented angioplasty patients with incomplete revascularization showed a significantly lower event-free survival than stented patients with complete revascularization (i.e., freedom from death, myocardial infarction, cerebrovascular accident and repeat revascularization) (69.4% vs. 76.6%; p < 0.05). This difference was due to a higher incidence of subsequent bypass procedures (10.0% vs. 2.0%; p < 0.05). Conversely, at one year, bypass surgery patients with incomplete revascularization showed only a marginally lower event-free survival rate than those with complete revascularization (87.8% vs. 89.9%). CONCLUSIONS: Complete revascularization was more frequently accomplished by bypass surgery than by stent implantation. One year after bypass, there was no significant difference in event-free survival between surgically treated patients with complete revascularization and those with incomplete revascularization, but patients randomized to stenting with incomplete revascularization had a greater need for subsequent bypass surgery. http://repub.eur.nl/res/pub/4798/ 2002-02-06T00:00:00Z OBJECTIVES: We sought to investigate the clinical benefit of additional stent implantation after achieving an optimal result of balloon angioplasty (BA) in long coronary lesions (>20 mm). BACKGROUND: Long coronary lesions are associated with increased early complications and late restenosis after BA. Stenting improves the early outcome, but stent restenosis is also related to both lesion length and stent length. METHODS: A total of 437 patients with a single native lesion 20 to 50 mm in length were included and underwent BA, using long balloons matched to lesion length and vessel diameter (balloon/artery ratio 1.1) to achieve a diameter stenosis (DS) <30% by on-line quantitative coronary angiography (QCA). "Bail-out stenting" was performed for flow-limiting dissections or >50% DS. Patients in whom an optimal BA result was achieved were randomized to additional stenting (using NIR stents) or no stenting. The primary end point was freedom from major adverse cardiac events (MACE) at nine months, and core laboratory QCA was performed on serial angiograms. RESULTS: Bailout stenting was necessary in 149 patients (34%) and was associated with a significantly increased risk of peri-procedural infarction (p < 0.02). Among the 288 randomized patients, the mean lesion length was 27+/-9 mm, and the vessel diameter was 2.78+/-0.52 mm. The procedural success rate was 90% for the 143 patients assigned to BA alone (control group), as compared with 93% in the 145 patients assigned to additional stenting (stent group), which resulted in a superior early minimal lumen diameter (0.54 mm, p < 0.001) and led to reduced angiographic restenosis (27% vs. 42%, p = 0.022). Freedom from MACE at nine months was 77% in both groups. CONCLUSIONS: A strategy of provisional stenting for long coronary lesions led to bailout stenting in one-third of patients, with a threefold increase in peri-procedural infarction. Additional stenting yielded a lower angiographic restenosis rate, but no reduction in MACE at nine months. http://repub.eur.nl/res/pub/9837/ 2002-02-05T00:00:00Z BACKGROUND: Radioactive stents with an activity of 0.75 to 12 microCi have shown >40% edge restenosis due to neointimal hyperplasia and negative remodeling. This trial evaluated whether radioactive Cold Ends stents might resolve edge restenosis by preventing remodeling at the injured extremities. METHODS AND RESULTS: The 25-mm long (15-mm radioactive center and 5-mm nonradioactive ends) Cold Ends stents had an activity of 3 to 12 microCi at implantation. Forty-three stents were implanted in 43 patients with de novo native coronary artery disease. Two procedural, 1 subacute, and 1 late stent thrombosis occurred. A restenosis rate of 22% was observed with a shift of the restenosis, usually occurring at the stent edges of radioactive stents, into the Cold Ends stents. The most severe restenosis occurred at the transition zone from radioactive to nonradioactive segments, a region located in dose fall-off. CONCLUSION: Cold Ends stents did not resolve edge restenosis. http://repub.eur.nl/res/pub/9952/ 2002-01-01T00:00:00Z BACKGROUND: The goal of this intravascular ultrasound investigation was to provide a more detailed morphological analysis of the local biological effects of the implantation of a sirolimus-eluting stent compared with an uncoated stent. METHODS AND RESULTS: In the RAVEL trial, 238 patients with single de novo lesions were randomized to receive either an 18-mm sirolimus-eluting stent (Bx VELOCITY stent, Cordis) or an uncoated stent (Bx VELOCITY stent). In a subset of 95 patients (sirolimus-eluting stent=48, uncoated stent=47), motorized intravascular ultrasound pullback (0.5 mm/s) was performed at a 6-month follow-up. Stent volumes, total vessel volumes, and plaque-behind-stent volumes were comparable. However, the difference in neointimal hyperplasia (2+/-5 versus 37+/-28 mm3) and percent of volume obstruction (1+/-3% versus 29+/-20%) at 6 months between the 2 groups was highly significant (P<0.001), emphasizing the nearly complete abolition of the proliferative process inside the drug-eluting stent. Analysis of the proximal and distal edge volumes showed no significant difference between the 2 groups in external elastic membrane or lumen and plaque volume at the proximal and distal edges. There was also no evidence of intrastent thrombosis or persisting dissection at the stent edges. Although there was a higher incidence of incomplete stent apposition in the sirolimus group compared with the uncoated stent group (P<0.05), it was not associated with any adverse clinical events at 1 year. CONCLUSIONS: Sirolimus-eluting stents are effective in preventing neointimal hyperplasia without creating edge effect and without affecting the plaque burden behind the struts. http://repub.eur.nl/res/pub/9962/ 2002-01-01T00:00:00Z AIMS: The BRIE trial is a registry evaluating the safety and performance of (90)Sr delivered locally (Beta-Cath TM system of Novoste) to de-novo and restenotic lesions in patients with up to two discrete lesions in different vessels. METHODS AND RESULTS: In total, 149 patients (175 lesions) were enrolled; 62 treated with balloons and 113 with stents. The restenosis rate, the minimal luminal diameter and the late loss were determined in three regions of interest: (a) in a subsegment of 5mm containing the original minimal luminal diameter pre-intervention termed target segment; (b) the irradiated segment, 28 mm in length, and (c) the entire analysed segment, 42 mm in length, termed the vessel segment. Binary restenosis was 9.9% for the target segment, 28.9% for the irradiated segment, and 33.6% for the vessel segment. These angiographic results include 5.3% total occlusions. Excluding total occlusions binary restenosis was 4.9%, 25% and 29.9%, respectively. At 1 year the incidence of major adverse cardiac events placed in a hierarchical ranking were: death 2%, myocardial infarction 10.1%, CABG 2%, and target vessel revascularization 20.1%. The event-free survival rate was 65.8%. Non-appropriate coverage of the injured segment by the radioactive source termed geographical miss affected 67.9% of the vessels, and increased edge restenosis significantly (16.3% vs 4.3%, P=0.004). It accounted for 40% of the treatment failures. CONCLUSION: The results of this registry reflect the learning process of the practitioner. The full therapeutic potential of this new technology is reflected by the restenosis rate at the site of the target segment. It can only be unravelled once the incidence of late vessel occlusion and geographical miss has been eliminated by the prolonged use of thienopyridine, the appropriate training of the operator applying this new treatment for restenosis prevention, and the use of longer sources. http://repub.eur.nl/res/pub/4823/ 2001-09-22T00:00:00Z Abstract OBJECTIVES: We sought to assess whether coronary stents have modified the predictive value of demographic, clinical and quantitative coronary angiographic (QCA) predictors of coronary restenosis. BACKGROUND: A systematic analysis in a large cohort of registries and randomized trials of the percutaneous transluminal coronary angioplasty (PTCA) and stent era has never been performed. METHODS: A total of 9,120 treated lesions in 8,156 patients included in nine randomized trials and 10 registries, with baseline, post-procedural and six-month follow-up QCA analyses, were included in this study. Predictors of restenosis were identified with univariate and multivariate logistic regression analyses. Interaction terms were introduced in the regression equation to evaluate whether the predictors of restenosis were common to both eras or specific for either one of the revascularization techniques. RESULTS: The restenosis rate was 35% after PTCA and 19% after angioplasty with additional stenting. In the univariate analysis, favorable predictors were previous coronary artery bypass graft surgery (CABG), stent use, stent length and a large pre-procedural minimal lumen diameter (pre-MLD); unfavorable predictors were weight, body mass index, diabetes mellitus, multi-vessel disease, lesion length and a high residual post-procedural diameter stenosis (post-DS). Predictors specific for the PTCA population were a large post-procedural MLD (post-MLD) as favorable and a severe pre-procedural DS (pre-DS) as unfavorable. Favorable predictors specific for the stent population were a large post-MLD and a large pre-procedural reference diameter (pre-RD). In the multivariate analysis, the best model included the following favorable predictors: stent use, a large post-MLD, previous CABG and the interaction term between stent use and a large post-MLD; unfavorable predictors were lesion length and diabetes mellitus. CONCLUSIONS: There are no major differences in demographic and clinical predictors of coronary restenosis between PTCA and stent populations. In the modern (stent) era, a severe pre-DS is no longer an unfavorable predictor of restenosis. Still important, but more so in the stent population, is a large post-MLD (optimal result). Finally, a larger pre-RD became a favorable predictor with the advent of stenting. http://repub.eur.nl/res/pub/4821/ 2001-09-12T00:00:00Z Aims To prospectively evaluate the influence of stent length on 6 month clinical and angiographic outcome, in patients with native coronary lesions up to 45mm in length, undergoing elective Magic Wallstent implantation. Methods and Results On the basis of pre-procedural angiography, 276 patients (aged 61·3±10·2 years; 78·6% male; 41·7% unstable angina) with a total of 302 lesions were prospectively assigned to one of five different length categories of Magic Wallstent. Angiography in multiple matched projections before and after implantation and at 6 months follow-up was analysed at the core laboratory. Primary end-points for the efficacy analysis were cumulative incidence of major adverse cardiac events and quantitative coronary angiography analysis 6 months after stent implantation. Magic Wallstent implantation was successful in 301 of 302 lesions and in 98·6% a residual stenosis <20% by online quantitative coronary angiography was achieved. At 30 days, 6·2% (1·8% subacute occlusion) of patients had experienced major adverse cardiac events, 27·5% at 6 months and 30·4% at 9 months. Angiographic restenosis occurred in 37%. Restenosis rates for the mini, extra-short, short, medium and long Wallstent groups were 25·9%, 25%, 22·6%, 36·2% and 67·5%, respectively. Multivariate analysis revealed stent length to be independently associated with greater angiographic restenosis and major adverse cardiac events. Conclusions While shorter Magic Wallstents provided late outcomes comparable with short balloon-expandable stents, excessive restenosis with longer Wallstents should obviate their use in elective percutaneous intervention. Long coronary lesions provide a challenging substrate for emerging antirestenosis therapies, such as stent coatings and brachytherapy. http://repub.eur.nl/res/pub/4841/ 2001-01-01T00:00:00Z The Cordis tantalum coil stent was assessed in a nonrandomized multicenter trial: 275 patients with stable or unstable angina were entered. Clinical follow-up was for 1 year, with repeat angiography at 6 months. The major adverse cardiac event rates (MACE) were 3%, 14%, and 17% at 1, 7, and 13 months, respectively. The procedural success rate was 96% and the subacute occlusion rate 1.5%, in a group of patients over 60% of whom had ACC/AHA type B2 or C lesions. The binary restenosis rate at 6 months was 17.3%. Minimum lumen diameter increased from 1.07 +/- 0.28 mm preprocedure to 2.93 +/- 0.34 mm poststenting and at 6 months was 1.99 +/- 0.69 mm. These results demonstrate that the Cordis tantalum stent can be used to treat complex lesions with good procedural success and low rates of subacute thrombosis and restenosis at 6 months. http://repub.eur.nl/res/pub/8449/ 2001-01-01T00:00:00Z BACKGROUND: Beta radiation is effective in reducing vascular neointimal proliferation in animals after injury caused by balloon angioplasty. However, the lowest dose that can prevent restenosis after coronary angioplasty has yet to be determined. METHODS: After successful balloon angioplasty of a previously untreated coronary stenosis, 181 patients were randomly assigned to receive 9, 12, 15, or 18 Gy of radiation delivered by a centered yttrium-90 source. Adjunctive stenting was required in 28 percent of the patients. The primary end point was the minimal luminal diameter six months after treatment, as a function of the delivered dose of radiation. RESULTS: At the time of follow-up coronary angiography, the mean minimal luminal diameter was 1.67 mm in the 9-Gy group, 1.76 mm in the 12-Gy group, 1.83 mm in the 15-Gy group, and 1.97 mm in the 18-Gy group (P=0.06 for the comparison of 9 Gy with 18 Gy), resulting in restenosis rates of 29 percent, 21 percent, 16 percent, and 15 percent, respectively (P=0.14 for the comparison of 9 Gy with 18 Gy). At that time, 86 percent of the patients had had no serious cardiac events. In 130 patients treated with balloon angioplasty alone, restenosis rates were 28 percent, 17 percent, 16 percent, and 4 percent, respectively (P=0.02 for the comparison of 9 Gy with 18 Gy). Among these patients, there was a dose-dependent enlargement of the lumen in 28 percent, 50 percent, 45 percent, and 74 percent of patients, respectively (P<0.001 for the comparison of 9 Gy with 18 Gy). The rate of repeated revascularization was 18 percent with 9 Gy and 6 percent with 18 Gy (P=0.26). CONCLUSIONS: Intracoronary beta radiation therapy produces a significant dose-dependent decrease in the rate of restenosis after angioplasty. An 18-Gy dose not only prevents the renarrowing of the lumen typically observed after successful balloon angioplasty, but actually induces luminal enlargement. http://repub.eur.nl/res/pub/9300/ 2000-01-01T00:00:00Z BACKGROUND: In addition to its known properties as a competitive, nonselective beta and alpha-1 receptor blocker, carvedilol directly inhibits vascular myocyte migration and proliferation and exerts antioxidant effects that are considerably greater than those of vitamin E or probucol. This provides the basis for an evaluation of carvedilol for the prevention of coronary restenosis. METHODS AND RESULTS: In a prospective, double-blind, randomized, placebo-controlled trial, 25 mg of carvedilol was given twice daily, starting 24 hours before scheduled directional coronary atherectomy and continuing for 5 months after a successful procedure. The primary end point was the minimal luminal diameter as determined during follow-up angiography 26+/-2 weeks after the procedure. Of 406 randomized patients, 377 underwent attempted atherectomy, and in 324 (88.9%), a </=50% diameter stenosis was achieved without the use of a stent. Evaluable follow-up angiography was available in 292 eligible patients (90%). No differences in minimal luminal diameter (1.99+/-0.73 mm versus 2.00+/-0.74 mm), angiographic restenosis rate (23.4% versus 23.9%), target lesion revascularization (16.2 versus 14.5), or event-free survival (79.2% versus 79.7%) between the placebo and carvedilol groups were observed at 7 months. CONCLUSIONS: The maximum recommended daily dose of the antioxidant and beta-blocker carvedilol failed to reduce restenosis after successful atherectomy. These findings are in contrast to those of the Multivitamins and Probucol Trial, which raises doubts regarding the validity of the interpretation that restenosis reduction by probucol was via antioxidant effects. The relationship between antioxidant agents and restenosis remains to be elucidated. http://repub.eur.nl/res/pub/5048/ 1996-02-01T00:00:00Z Objectives. This study sought to determine the 1-year clinical follow-up of patients included in the Benestent trial. Background. The Benestent trial is a randomized study comparing elective Palmaz-Schatz stent implantation with balloon angioplasty in patients with stable angina and a de novo coronary artery lesion. Seven-month follow-up data have shown a decreased rate of restenosis and fewer clinical events in the stent group. It is not established whether this favorable clinical outcome is maintained for longer periods or whether coronary stenting defers restenosis and its subsequent clinical manifestations. Methods. To clarify this uncertainty, we updated clinical information on all but 1 of 516 patients enrolled in the Benestent trial (257 in balloon group, 259 in stent group) at least 12 months after the intervention. Major clinical events (primary clinical end point) were tabulated according to the intention to treat principle myocardial infarction, the need for bypass surgery or a further percutaneous intervention in the previously treated lesion. Results. After 1 year, no significant differences in mortality (1.2% vs. 0.8%), stroke (0.0% vs 0.8%), myocardial infarction (5.0% vs. 4.2%) or coronary bypass graft surgery (6.9% vs. 5.1%) were found between the stent and balloon angioplasty groups, respectively. However, the requirement for a repeat angioplasty procedure was significantly lower in the stent group (10%) than the balloon angioplasty group (21%, relative risk [RR] 0.49, 95% confidence interval [CI] 0.31 to 0.75, p = 0.001), and overall primary end points were less frequently reached by stent group patients (23.2%) than those in the balloon group (31.5%, RR 0.74, 95% CI 0.55 to 0.98, p = 0.04). No differences were found between groups with respect to functional class angina and prescribed medication at the time of follow-up. Conclusions. These clinical follow-up data show that the benefit of elective native coronary artery stenting in patients with stable angina is maintained to at least 1 year after the procedure and results in a significantly reduced requirement for repeat intervention. http://repub.eur.nl/res/pub/4599/ 1994-01-01T00:00:00Z OBJECTIVES. To characterize predictors of restenosis after successful directional atherectomy, we reviewed the clinical, angiographic and procedural data obtained during 132 consecutive procedures. METHODS. Clinical and angiographic follow-up data were obtained in a prospectively collected and consecutive series of 125 patients who underwent 132 atherectomy procedures for de novo (89%) or restenotic (11%) lesions in native coronary arteries. Restenosis was assessed clinically and by quantitative coronary angiography. A dual approach to data analysis was taken to gain insight into factors affecting the clinical outcome and vessel wall healing response. Therefore, multivariate analysis was performed to 1) determine the correlates of residual lumen diameter at follow-up (angiographic outcome), and 2) characterize the determinants of the late lumen loss (renarrowing process). RESULTS. Clinical and angiographic follow-up data after successful atherectomy were obtained in 100% and 95%, respectively. Atherectomy achieved an acute lumen gain of 1.28 +/- 0.48 mm (mean +/- SD), resulting in a minimal lumen diameter of 2.44 +/- 0.47 mm. At follow-up, the minimal lumen diameter decreased to 1.78 +/- 0.64 mm. The angiographic restenosis rate was 28% if the traditional 50% stenosis cutoff criterion was applied. Larger vessel size and postatherectomy minimal lumen diameter and right coronary or left circumflex artery lesions were independent predictors of a larger minimal lumen diameter (angiographic outcome). Lumen loss during follow-up (renarrowing process) was independently predicted by relative lumen gain and preprocedural minimal lumen diameter. CONCLUSIONS. In analyzing the long-term results of new interventional techniques such as directional atherectomy, the late lumen loss during follow-up (renarrowing process), which is characterized by the vessel wall healing response after an intervention, should be considered together with the residual lumen diameter at follow-up (clinical outcome). It is clear that whereas improved clinical outcome is associated with larger vessel size and postprocedural lumen diameter and non-left anterior descending artery location, greater relative gain at intervention is predictive of more extensive lumen renarrowing. http://repub.eur.nl/res/pub/4504/ 1993-01-01T00:00:00Z An attempt was made to assess the mechanism of directional coronary atherectomy using different methods of analysis. Quantitative coronary angiography was used as the gold standard to assess the immediate results of atherectomy, and a comparative quantitative analysis of atherectomy and balloon angioplasty was made. To determine whether the post-atherectomy cross-sectional area is close to a circle, we compared the area measurements obtained by edge detection with those obtained by videodensitometry. Finally, the extent of a 'Dotter' effect was established by quantitative angiography following crossing the stenosis with the atherectomy device. For the purpose of this study, the results of the first 113 successful atherectomy procedures were reviewed. In matched lesions, directional atherectomy induced a greater increase in minimal luminal diameter than balloon angioplasty (1.6 mm vs 0.8 mm; P < 0.0001). However, this luminal improvement is due to a substantial 'Dotter' effect induced by the bulky atherectomy device. Following atherectomy, only a slight difference in cross-sectional area measurements between edge detection and videodensitometry (mean difference: 0.28 mm2) was found. Histologic examination of an atherectomized coronary artery showed a near-circular postatherectomy area geometry. In conclusion, directional atherectomy is a very effective device with a substantially better initial result than balloon angioplasty. However, insertion of this bulky device itself causes an important 'Dotter' effect. http://repub.eur.nl/res/pub/4531/ 1993-01-01T00:00:00Z http://repub.eur.nl/res/pub/4532/ 1993-01-01T00:00:00Z Background. The renarrowing process after successful percutaneous transluminal coronary angioplasty (PTCA) is now believed to be caused by a response-to-injury vessel wall reaction. The magnitude of this process can be assessed by the change in minimal lumen diameter (MLD) at follow-up angiography. The aim of the present study was to find independent patient-related, lesion-related, and procedure-related risk factors for this luminal narrowing process. A model that accurately predicts the amount of luminal narrowing could be an aid in patient or lesion selection for the procedure, and it could improve assessment of medium-term (6 months) prognosis. Modification or control of the identified risk factors could reduce overall restenosis rates, and it could assist in the selection of patients at risk for a large loss in lumen diameter. This population could then constitute the target population for pharmacological intervention studies. Methods and Results. Quantitative angiography was performed on 666 successfully dilated lesions at angioplasty and at 6-month follow-up. Multivariate linear regression analysis was performed to obtain variables with an independent contribution to the prediction of the absolute change in minimal lumen diameter. Diabetes mellitus, duration of angina <2.3 months, gain in MLD at angioplasty, pre-PTCA MLD, lesion length 26.8 mm, and thrombus after PTCA were independently predictive of change in MLD. Overall prediction of the model was poor, however, percentage-correct classification for a predicted change between -0.1 to -0.4 mm was approximately 10%. Lesions showing no change or regression (change > -0.1 mm) and lesions showing large progression (< -0.4 mm) were more predictable (correct classification, 59.5% and 49.7%, respectively). Conclusions. Renarrowing after successful PTCA as determined with contrast angiography is a process that cannot be accurately predicted by simple clinical, morphological, and lesion characteristics. http://repub.eur.nl/res/pub/4466/ 1992-01-01T00:00:00Z Directional coronary atherectomy has been introduced as an alternative to conventional balloon angioplasty when treating coronary artery stenoses with complex lesion morphology. To determine the immediate efficacy of coronary atherectomy in patients with such lesions, the first 113 attempts at directional atherectomy in two centres using quantitative angiography were reviewed in 105 patients. The lesions were classified as complex stenosis since 95% had a symmetry index less than 1.0, a length of 6.83 +/- 2.55 mm on average and an area of plaque of 9.77 +/- 6.69 mm2. Procedural success defined as a residual stenosis less than or equal to 50% after tissue retrieval was obtained in 90 (85.7%) of 105 patients. The primary angioplastic success rate, combining atherectomy and balloon angioplasty in case of failed attempt of atherectomy was 95.2%. Coronary atherectomy was unsuccessful in five patients; three were referred for emergency coronary artery bypass grafting. Major complications (death, emergency surgery and transmural infarction) were encountered in 5.7% of the patients. Assessed by quantitative coronary analysis, a residual minimal luminal diameter of 2.42 +/- 0.52 mm and a diameter stenosis of 26 +/- 12% were obtained immediately after directional coronary atherectomy. We conclude that directional coronary atherectomy is particularly suitable for the treatment of stenosis with complex lesion morphology and is associated with acceptable complication rates. Randomized trials comparing atherectomy with balloon angioplasty are warranted to clarify the role of atherectomy in the treatment of lesions in the proximal part of the three major epicardial coronary arteries. http://repub.eur.nl/res/pub/4470/ 1992-01-01T00:00:00Z BACKGROUND. Cilazapril is a novel angiotensin converting enzyme inhibitor with antiproliferative effects in the rat model after balloon injury. METHODS AND RESULTS. We conducted a randomized, double-blind placebo-controlled trial to assess the effect of cilazapril in angiographic restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received cilazapril 2.5 mg in the evening after successful PTCA and 5 mg b.i.d. for 6 months or matched placebo. In addition, all patients received aspirin for 6 months. Coronary angiograms before PTCA, after PTCA, and at 6-month follow-up were quantitatively analyzed. In 94% of 735 recruited patients, PTCA was successful and all inclusion and exclusion criteria were met. For the per-protocol analysis, quantitative angiography after PTCA and at follow-up was available in 595 patients who complied with the treatment regimen (309 control, 286 cilazapril). The mean difference in minimal coronary lumen diameter between post-PTCA and follow-up angiogram (primary end point) was -0.29 +/- 0.49 mm in the control group and - 0.27 +/- 0.51 mm in the cilazapril group. Clinical events during 6- month follow-up, analyzed on an intention-to-treat basis, were ranked according to the most serious clinical event ranging from death (control, two; cilazapril, three), nonfatal myocardial infarction (control, eight; cilazapril, 5), coronary revascularization (control, 51; cilazapril, 53), or recurrent angina requiring medical therapy (control, 67; cilazapril, 68) to none of the above (control, 224; cilazapril, 212). There were no significant differences in ranking. CONCLUSIONS. Long-term angiotensin converting enzyme inhibition with cilazapril in a dose of 5 mg b.i.d. does not prevent restenosis and does not favorably influence the overall clinical outcome after PTCA. http://repub.eur.nl/res/pub/4480/ 1992-01-01T00:00:00Z OBJECTIVES: The objective of this study was to examine the relation between an angiographically visible coronary dissection immediately after successful coronary balloon angioplasty and a subsequent restenosis and long-term clinical outcome. BACKGROUND. The study population comprised all 693 patients who participated in the MERCATOR trial (randomized, double-blind, placebo-controlled restenosis prevention trial of cilazapril, 5 mg two times a day). METHODS. Cineangiographic films were processed and analyzed at a central angiographic core laboratory, without knowledge of clinical data, with use of an automated interpolated edge detection technique. Dissection was judged according to the National Heart, Lung, and Blood Institute classification. Angiographic follow-up was obtained in 94% of patients with 778 lesions. Two approaches were used to assess the restenosis phenomenon: 1) categoric, using the traditional cutoff criterion of greater than 50% diameter stenosis at follow-up, and 2) continuous, defined as absolute change in minimal lumen diameter (mm) between the postcoronary angioplasty and follow-up, adjusted for the vessel size (relative loss). Clinical outcome was ranked according to the most serious adverse clinical event per patient during the 6-month follow-up period, ranging from death, nonfatal myocardial infarction, coronary revascularization and recurrent angina requiring medical therapy to none of these. RESULTS. Dissection was present in 247 (32%) of the 778 dilated lesions. The restenosis rate was 29% in lesions with and 30% in lesions without dissection (relative risk 0.97; 95% confidence interval 0.77 to 1.23). The relative loss in both groups was 0.10 (mean difference 0; 95% confidence interval -0.03 to 0.03). Clinical outcome ranged from death in 4 patients (0.9%) without dissection and 1 patient (0.4%) with dissection; nonfatal myocardial infarction in 4 (0.9%) without and 8 (3.2%) with dissection; coronary revascularization in 73 (16.6%) without and 32 (12.7%) with dissection; recurrent angina requiring medical therapy in 88 (20%) without and 47 (18.7%) with dissection to no serious adverse event in 272 (61.7%) without and 114 (65.1%) with dissection. CONCLUSIONS. These data indicate that a successfully dilated coronary lesion with an angiographically visible dissection is no more likely to develop restenosis, and is not associated with a worse clinical outcome, at 6-month follow-up than is a dilated lesion without visible dissection on the post-balloon angioplasty angiogram. http://repub.eur.nl/res/pub/4435/ 1991-01-01T00:00:00Z BACKGROUND. GR32191B is a novel thromboxane A2-receptor antagonist with potent antiagregational and antivasoconstrictive properties. We have conducted a randomized, double-blind placebo-controlled trial to study its usefulness in restenosis prevention. METHODS AND RESULTS. Patients received either GR32191B (80 mg orally before angioplasty and 80 mg/day orally for 6 months) or 250 mg i.v. aspirin before angioplasty and placebo for 6 months. Coronary angiograms before angioplasty, after angioplasty, and at 6-month follow-up were quantitatively analyzed. Angioplasty was attempted in 697 patients. For efficacy analysis, quantitative angiography at follow-up was available in 522 compliant patients (261 in each group). Baseline clinical and angiographic parameters did not differ between the two treatment groups. The mean difference in coronary diameter between postangioplasty and follow-up angiogram (primary end point) was -0.31 +/- 0.54 mm in the control group and -0.31 +/- 0.55 mm in the GR32191B group. Clinical events during 6-month follow-up, analyzed on intention-to-treat basis, were ranked according to the highest category on a scale ranging from death (control, six; GR32191B, four) to nonfatal infarction (control, 22; GR32191B, 18), bypass grafting (control, 19; GR32191B, 22) and repeat angioplasty (control, 52; GR32191B, 48). No significant difference in ranking was detected. Six months after angioplasty, 75% of patients in the GR32191B group and 72% of patients in the control group were symptom free. CONCLUSIONS. Long-term thromboxane A2-receptor blockade with GR32191B does not prevent restenosis and does not favorably influence the clinical course after angioplasty. http://repub.eur.nl/res/pub/4181/ 1986-01-01T00:00:00Z The effect of repeated (3 to 10 second) and transient (15 to 75 second) abrupt coronary occlusion on the global and regional chamber stiffness was studied in nine patients undergoing angioplasty of a single proximal left anterior descending coronary artery stenosis. The left ventricular high fidelity pressure and volume relation was obtained before and after the procedure as well as during coronary occlusion, after 20 seconds (n = 9) and after 50 seconds (n = 5). During ischemia, there was an upward shift of the pressure-volume relation. The nonlinear simple elastic constant of chamber stiffness increased from 0.0273 +/- 0.017 before angioplasty (mean +/- SD) to 0.0621 +/- 0.026 after 20 seconds of occlusion (p less than 0.05) and 0.0605 +/- 0.015 after 50 seconds of occlusion (p less than 0.01). In five patients, the postangioplasty value remained higher than the control value, but at the group level the mean value (0.0529 +/- 0.037) was not statistically different. The regional stiffness was determined from the changes in the length of six segmental radii during diastole, from the lowest diastolic to the end-diastolic pressure. The regional constant of elastic stiffness was unaffected in the nonischemic zone. In the adjacent and ischemic zones, the regional stiffness was increased during occlusion (p less than 0.05). These regional abnormalities in diastolic function persisted at the time of postangioplasty measurements, 12 minutes after the end of the procedure. This suggests that recovery of normal diastolic function after repeated ischemic injuries is delayed after restoration of normal blood flow and systolic function. http://repub.eur.nl/res/pub/4183/ 1986-01-01T00:00:00Z Dopexamine increases inotropic state and rate of relaxation independent of changes in heart rate. Dopexamine has a chronotropic effect and results in a decrease in systemic vascular resistance. Dopexamine has a spectrum of action that should be useful in patients with severe heart failure. http://repub.eur.nl/res/pub/4184/ 1986-01-01T00:00:00Z The effect of early myocardial reperfusion (within 4 hours after onset of symptoms) on regional left ventricular function in patients with acute myocardial infarction has been quantitated by analysis of segmental wall motion. Of 533 patients randomized either to conventional coronary care unit therapy or to a reperfusion strategy, in 332 high quality angiograms were obtained 2 to 8 weeks after the onset of myocardial infarction. In those assigned to thrombolytic therapy, angiographic data were also available after acute reperfusion. Analysis on an "intention to treat" basis revealed significant preservation of left ventricular function after thrombolytic therapy (ejection fraction 53%) compared with conventional treatment (ejection fraction 47%). In addition, wall motion analysis showed significant improvement of regional function in the infarct zone in both inferior and anterior infarction. In addition, significant changes occurred in regional function of the remote "noninfarct zone" in the acute as well as the chronic stage. It is concluded that improved regional and global left ventricular function can be achieved with early reperfusion and that this is the likely explanation for the reduction of early and late mortality after thrombolysis observed in this study. http://repub.eur.nl/res/pub/4205/ 1986-01-01T00:00:00Z This study is a retrospective analysis of the efficacy of percutaneous transluminal coronary angioplasty of the ischaemia-related vessel in patients with unstable angina. Forty-three patients had multivessel disease with dilatation of the ischaemia-related vessel only (group I; partial revascularization) while 111 patients had single vessel disease only (group II; total revascularization). The initial success rate in both groups was identical (88 versus 88%). The need for emergency coronary artery bypass surgery was similar in the two groups (group I 12% versus group II 9%; NS). The total post PTCA myocardial infarction rate (despite urgent CABG) was also similar in the two groups (group I 9% versus group II 10%; NS). The results of electrocardiographic exercise testing and Thallium-201 scintigraphy provide objective evidence for incomplete revascularization in group I. The maximum workload achieved was lower, and the frequency of exercise induced angina, ST-segment depression and reversible perfusion defect was higher than in group II. Moreover, at 6 months follow-up the recurrence rate of angina pectoris rate was higher in group I than in group II (29% versus 16% P less than 0.05). It is concluded that dilatation of the ischaemia related vessel only in patients with unstable angina and multivessel disease is as effective in the management of the acute phase of unstable angina as is dilatation of the ischaemia related vessel in patients with single vessel disease. However, due to only partial revascularization the recurrence rate of angina pectoris is higher. http://repub.eur.nl/res/pub/4225/ 1986-01-01T00:00:00Z The effect of reperfusion achieved by early intracoronary streptokinase in acute myocardial infarction on left ventricular function was studied in 533 patients enrolled in a prospective randomised multicentre study. Two hundred and sixty four patients were allocated to conventional treatment and 269 patients to thrombolysis. At the end of the procedure patency of the infarct related vessel was achieved in 198 (85%) of 234 patients in whom coronary angiography was performed. The median interval from onset of symptoms till the angiographic documentation of patency was 200 minutes. Data were analysed according to the original treatment allocation. Global left ventricular ejection fraction was determined by radionuclide angiography in 418 patients within two days of admission, in 361 patients after two weeks, and in 307 patients after three months. Global left ventricular function remained unchanged throughout the observation period in the control group, whereas it improved during the first two weeks in patients allocated to thrombolytic treatment. Improved function in these patients persisted up to three months after the infarction. Global left ventricular ejection fraction was significantly better in the thrombolysis group than in the control group at two days, two weeks, and at three months. In patients with anterior myocardial infarction the left ventricular ejection fraction was 9% better than in the control group at two weeks and at three months. In the patients with inferior myocardial infarction differences between the two treatment groups were smaller because of photon attenuation within the body. Angiographic evidence suggested that the improvement in function seen after thrombolysis is indeed associated with the patency of the infarct related artery. http://repub.eur.nl/res/pub/4134/ 1985-01-01T00:00:00Z A computer-assisted technique has been developed to assess absolute coronary arterial dimensions from 35 mm cineangiograms. The boundaries of optically magnified and video-digitized coronary segments and the intracardiac catheter are defined by automated edge-detection techniques. Contour positions are corrected for pincushion distortion. The accuracy and precision of the edge detection procedure as assessed from cinefilms of contrast-filled acrylate (Perspex) models were -30 and 90 micrometers, respectively. The variability of the analysis procedure itself in terms of absolute arterial dimensions was less than 0.12 mm, and in terms of percentage arterial narrowing for coronary obstructions less than 2.74%. Short-, medium-, and long-term variability measurements were assessed from repeated coronary angiographic examinations performed 5 min, 1 hr, and 90 days apart, respectively. For all studies the mean differences in absolute diameters were less than 0.13 mm. The variability in obstruction diameter ranged from 0.22 mm for the best-controlled study (medium-term) to 0.36 mm for the least-controlled study (long-term); variability in reference diameter ranged from 0.15 to 0.66 mm, respectively. It is concluded that the biological variations are a source of major concern and that further attempts toward standardization of the angiographic procedure are seriously needed. http://repub.eur.nl/res/pub/4135/ 1985-01-01T00:00:00Z To evaluate, during cardiac catheterization, what constitutes a physiologically significant obstruction to blood flow in the human coronary system, computer-based quantitative analysis of coronary angiograms was performed on the angiograms of 31 patients with isolated disease of the proximal left anterior descending coronary artery. The angiographic severity of stenosis was compared with the transstenotic pressure gradient measured with the dilation catheter during angioplasty and with the results of exercise thallium scintigraphy. A curvilinear relationship was found between the pressure gradient across the stenosis (normalized for the mean aortic pressure) and the residual minimal area of obstruction (after subtracting the area of the angioplasty catheter). This relationship was best fitted by the equation: normalized mean pressure gradient = a + b . log [obstruction area], r = .74. The measurements of the percent area of stenosis (cutoff 80%) and of the transstenotic pressure gradient (cutoff 0.30) obtained at rest correctly predicted the occurrence of thallium perfusion defects induced by exercise in 83% of the patients. http://repub.eur.nl/res/pub/4136/ 1985-01-01T00:00:00Z Restenosis of the dilated vessel after percutaneous transluminal coronary angioplasty can be detected by non-invasive procedures but their ability to predict later restenosis soon after a successful angioplasty as well as recurrence of angina has not been assessed. A maximal exercise test and myocardial thallium perfusion scintigraphy were, therefore, performed in 91 asymptomatic patients a median of 5 weeks after they had undergone a technically successful angioplasty. Primary success of the procedure was confirmed by the decrease in percentage diameter stenosis from 64(12)% to 30(13)% as measured from the coronary angiograms and in the trans-stenotic pressure gradient (normalised for mean aortic pressure) from 0.61(0.16) to 0.17(0.09). A clinical follow up examination (8.6(4.9) months later) was carried out in all patients and a late coronary angiogram obtained in 77. The thallium perfusion scintigram showing the presence or absence of a reversible defect was highly predictive for restenosis whereas the exercise test was not. The positive predictive value of an abnormal scintigram was 82% compared with 60% for the exercise test (ST segment depression/or angina or both at peak workload). Angina or a new myocardial infarction occurred in 60% of patients with abnormal and in 21% of patients with normal scintigrams. http://repub.eur.nl/res/pub/4137/ 1985-01-01T00:00:00Z The value of exercise testing and thallium scintigraphy in predicting recurrence of angina pectoris and restenosis after a primary successful transluminal coronary angioplasty (PTCA) was prospectively evaluated. In 89 patients, a symptom-limited exercise electrocardiogram (ECG) and thallium scintigraphy were performed 4 weeks after they had undergone successful PTCA. Thereafter, the patients were followed for 6.4 +/- 2.5 months (mean +/- standard deviation) or until recurrence of angina. They all underwent a repeat coronary angiography at 6 months or earlier if symptoms recurred. PTCA was considered successful if the patients had no symptoms and if the stenosis was reduced to less than 50% of the luminal diameter. Restenosis was defined as an increase of the stenosis to more than 50% luminal diameter. The ability of the thallium scintigram (presence of a reversible defect) to predict recurrence of angina was 66%, vs 38% for the exercise ECG (ST-segment depression or angina at peak workload). Restenosis was predicted in 74% of patients by thallium scintigraphy, but only in 50% of patients by the exercise ECG. Thus, thallium scintigraphy was highly predictive but the exercise ECG was not (p less than 0.005). These results suggest that restenosis had occurred to some extent already at 4 weeks after the PTCA in most patients in whom it was going to occur. http://repub.eur.nl/res/pub/4138/ 1985-01-01T00:00:00Z Of 652 consecutive patients referred for coronary angioplasty between September 1980 and March 1984, 49 patients presented with total or functional 'occlusion' of the involved vessel. Total vessel occlusion was defined as absent anterograde filling beyond the lesion. Functional occlusion was defined as faint, late anterograde opacification of the distal segment in the absence of a discernible luminal continuity. In 39 patients, the total or functional occlusion represented a progression, without acute myocardial infarction, of a previously diagnosed stenotic lesion. The maximal potential duration of occlusion was estimated to be 4 weeks or less in 21 patients, more than 4 to 8 weeks in 12, and more than 8 weeks in 16. Dilation of the occluded artery was attempted in the left anterior descending coronary artery in 30 patients, in the right coronary artery in 8, in the circumflex coronary in 7 and in 4 jumpgrafts. For the whole group, angioplasty was successful in 28 patients (57%). The primary success rate with the functionally occluded vessel (81%) was significantly higher than with the total occlusion (45%). In 33 patients with an occlusion estimated to be of 8 weeks or less, angioplasty was successful in 65%. In the 16 patients with an occlusion estimated to be of 8 weeks or less, angioplasty was successful in 65%. In the 16 patients with an occlusion estimated to be of more than 8 weeks duration, dilation was successful in 44%. Of the 21 patients in whom angioplasty was unsuccessful, 11 required surgery (1 urgent with persistent pain and ST elevation and 10 elective). Ten patients were maintained on medical treatment. Of the 28 patients in whom angioplasty was successful, 10 patients had recurrence of symptoms during follow-up (1-42 months). Four were kept on medical therapy, three required bypass surgery and three underwent repeat percutaneous transluminal coronary angioplasty (PTCA). After primary success, late angiographic studies obtained in 20 out of 28 patients showed reocclusion in 8. In conclusion, elective PTCA of totally occluded coronary arteries is feasible but the primary success rate is lower (57%) than that associated with conventional lesions. The long-term clinical results following successful angioplasty are satisfactory (64%), but the incidence of reocclusion is higher (40%). http://repub.eur.nl/res/pub/4146/ 1985-01-01T00:00:00Z -- http://repub.eur.nl/res/pub/4158/ 1985-01-01T00:00:00Z The hemodynamic effects of diltiazem were investigated in 15 patients with suspected coronary artery disease undergoing routine cardiac catheterization. Diltiazem was given in a high dose of 500 micrograms/kg over a period of 5 min and measurements made before and after drug administration during spontaneous heart rate and during matched atrial pacing. Spontaneous heart rate did not change (-5%; NS). Left ventricular (LV) systolic pressure decreased 24% (p less than 10(-6)) and LV end-diastolic pressure (LVEDP) did not change (-5%; NS). During coronary blood flow measurement, mean aortic pressure decreased 30% (p less than 10(-6)) as global (coronary sinus) and regional (great cardiac vein) coronary vascular resistance diminished with no change in coronary blood flow. Myocardial oxygen consumption decreased 19% (p less than 0.02). During matched pacing, although no change occurred in calculated systolic isovolumic indexes of contractility, end-systolic pressure-volume index decreased 15% (p less than 0.05). The time constant of isovolumic relaxation assessed by a biexponential model decreased. No net change occurred in either global or regional wall motion. In summary, high-dose diltiazem was administered safely to patients with coronary artery disease. It is concluded that, at this dose, diltiazem acted as a peripheral and coronary vasodilator. Hemodynamic changes consistent with a direct negative inotropic and chronotropic effect of the drug were observed. Myocardial oxygen consumption decreased with no change in coronary blood flow. http://repub.eur.nl/res/pub/4159/ 1985-01-01T00:00:00Z The effect of myocardial reperfusion on regional left ventricular function has been quantitated by analysis of segmental wall motion in 185 patients enrolled in a randomized trial comparing thrombolysis with conventional treatment in patients with acute myocardial infarction. When analyzing the hemodynamic data on an "intention to treat" basis we found a significant preservation of left ventricular function after thrombolytic therapy when compared to conventional treatment. In addition, the wall motion analysis showed that a significant improvement of regional function in the "infarct zone" was observed in inferior infarction as well as in anterior infarction, although significant changes in regional function of the remote "non infarct zone" were observed at the acute as well as at the chronic stage. However, our follow-up data indicate that as yet it has not been resolved whether this method of treatment does indeed improve prognosis in patients with acute myocardial infarction. Accordingly, we maintain the view that such invasive treatment should not be generally applied until more follow-up data become available from larger randomized trials. http://repub.eur.nl/res/pub/4160/ 1985-01-01T00:00:00Z The pressure gradient across coronary stenoses is measured routinely during angioplasty. Due to the finite size of the angioplasty catheter within the stenotic cross section, the remaining luminal area is further reduced and the transstenotic gradient may be overestimating the "true" pressure drop. This "true" pressure gradient can be approximated from the mean coronary blood flow and the stenosis geometry from theoretical models. Goal of this study was to assess the values and limitations of the in vivo measurements of the pressure gradient versus the calculated values. Therefore, flow in the great cardiac vein was measured in 13 patients before and/or after angioplasty of a proximal left anterior descending stenosis, not filled by collaterals. The Poiseuille and turbulent contributions to flow resistance were determined from stenosis geometry assessed by quantitative coronary angiography. A fourfold increase in the luminal area (from 0.7 mm2 pre- to 2.8 mm2 post angioplasty) was associated with a fourfold decrease in the in vivo measured transstenotic gradient (from 59 mm Hg pre- to 13 mm Hg post angioplasty). The occlusion area and the measured gradient were linearly correlated: gradient = 69-17 X occlusion area (r = 0.76). However, as expected, the transstenotic gradient systematically overestimated the theoretical gradient calculated from the laws of fluid dynamics. A nonlinear relation was found between the calculated gradient P and the occlusion area As: P = 15 X As-2 (r = 0.87). http://repub.eur.nl/res/pub/4175/ 1985-01-01T00:00:00Z The hemodynamic effects of nisoldipine were investigated in 16 patients with suspected coronary artery disease who underwent routine cardiac catheterization. Nisoldipine was given intravenously in a dose of 6 micrograms/kg over 3 minutes and measurements made before and after drug administration during spontaneous and matched atrial paced heart rate. During sinus rhythm, nisoldipine produced a significant increase in heart rate (19%, p less than 10(-5]. Left ventricular systolic pressure decreased 28% (p less than 10(-6) and left ventricular end-diastolic pressure did not change significantly (5%, difference not significant). Coronary sinus and great cardiac vein blood flow increased by 21% (p less than 0.02) and 25% (p less than 0.005), respectively, after nisoldipine administration. Simultaneously, mean aortic pressure decreased 33% (p less than 10(-6]; consequently, the global and regional coronary vascular resistances decreased by 50% (p less than 10(-4]. The decreases in global (-8%) and regional (-4%) myocardial oxygen consumption did not reach statistical significance. A 6% (not significant) increase in end-diastolic volume and an 11% (p less than 0.002) decrease in end-systolic volume resulted in an increase of 21% in stroke volume (p less than 10(-4] with a consistent increase in ejection fraction (+16%, p less than 10(-5]. Total systemic vascular resistance was reduced by 30% (p less than 0.0002). During spontaneous heart rate and matched atrial pacing, the time constant of isovolumic relaxation as assessed by a biexponential model, was significantly shortened.(ABSTRACT TRUNCATED AT 250 WORDS) http://repub.eur.nl/res/pub/4122/ 1984-01-01T00:00:00Z The response of left ventricular function, coronary blood flow, and myocardial lactate metabolism during percutaneous transluminal coronary angioplasty (PTCA) was studied in a series of patients undergoing the procedure. From four to six balloon inflation procedures per patient were performed with an average duration per occlusion of 51 +/- 12 sec (mean +/- SD) and a total occlusion time of 252 +/- 140 sec. Analysis of left ventricular hemodynamics in 19 patients showed that the relaxation parameters, peak negative rate of change in pressure, and early time constants of relaxation, responded earliest to short-term coronary occlusion (peak effect at 17 +/- 7 sec) while other parameters, such as peak pressure, left ventricular end-diastolic pressure, and peak positive rate of change in pressure, responded more gradually, suggesting a progressive depression of myocardial mechanics throughout the procedure. Left ventricular angiograms, available for 14 patients, indicated an early onset of asynchronous relaxation concurrent with the early response in peak negative dP/dt and the time constant of early relaxation. All hemodynamic functions fully recovered within minutes after the end of PTCA. Mean blood flow in the great cardiac vein and proximal coronary sinus and the hyperemic response were measured in 20 patients. Before PTCA mean flow in the great cardiac vein was 69 +/- 17 ml/min and in the coronary sinus it was 129 +/- 34 ml/min. Reactive hyperemia (great cardiac vein) was 55% after the first PTCA and 91% after the third. A more pronounced reaction was observed when the residual functional coronary stenosis was reduced in subsequent dilatations. Arteriovenous lactate difference appeared constant during the first two occlusions (control +0.11 mmol/liter, first PTCA -0.87 mmol/liter, and second PTCA -0.82 mmol/liter) and did not increase during subsequent occlusions. Within minutes after the procedure lactate balance was again positive, demonstrating the reversibility of the metabolic disturbances after repeated ischemia. The results of this study indicate that there is no permanent dysfunction of global or regional myocardial mechanics, myocardial blood flow, or lactate metabolism after PTCA with four to six coronary occlusions of 40 to 60 sec. http://repub.eur.nl/res/pub/4123/ 1984-01-01T00:00:00Z Cineangiograms of 138 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) were analyzed with a computer-based coronary angiography analysis system. The results before and after dilatation are presented. In a first study group (120 patients), the severity of the obstructive lesions derived from the automatically detected contours was evaluated in absolute terms and in percent-diameter reduction. In a second group of patients, 18 coronary lesions were selected for their extreme severity and symmetric aspect before angioplasty as assessed from multiple views. In the second group, the densitometric percent-area stenosis was used to assess the changes in cross-sectional area after PTCA and was compared with the circular percent-area stenosis computed from the diameter measurements. Before PTCA, a good agreement exists between the densitometric percent-area stenosis and the circular percent-area stenosis. After PTCA, important discrepancies between these 2 types of measurements are observed. It is suggested that these discrepancies in results after PTCA can be accounted for by asymmetric morphologic changes in luminal cross section, which cannot be assessed accurately from diameter measurements in a single-plane view. http://repub.eur.nl/res/pub/4125/ 1984-01-01T00:00:00Z The response of left ventricular function, was studied in a series of patients undergoing percutaneous transluminal coronary angioplasty (PTCA). From 4 to 6 balloon inflations procedures per patient were performed with an average duration per occlusion of 51 +/- 12 sec (mean +/- SD), total occlusion time 252 +/- 140 sec. Analysis of left ventricular (LV) haemodynamics showed that the relaxation parameters peak negative rate of change in pressure and the early time constant of relaxation responded earliest to acute coronary occlusion while other parameters such as peak pressure, LV end-diastolic pressure, and peak positive rate of change of pressure responded more gradually and suggested a progressive depression in myocardial mechanics during the entire procedure. LV angiogram available in 14 patients indicate an early onset of asynchronous relaxation concurrent with the early response in peak -dP/dt and the time constant of early relaxation. All haemodynamic parameters fully recovered within minutes after the end of PTCA. The results of this study indicate no permanent dysfunction to global or regional myocardial mechanics, after PTCA with 4 to 6 coronary occlusions each lasting 40 to 60 seconds. http://repub.eur.nl/res/pub/4088/ 1983-01-01T00:00:00Z -- http://repub.eur.nl/res/pub/5282/ 1983-01-01T00:00:00Z A fully automated procedure for the computation of left-ventricular ejection fraction (EF) from cardiac-gated Tc-99m blood-pool (GBP) scintigrams with fixed, dual, and variable ROI methods is described. By comparison with EF data from contrast ventriculography in 68 patients, the dual-ROI method (separate end-diastolic and end-systolic contours) was found to be the method of choice; processing time was 2 min. Success score of dual-ROI procedure was 92% as assessed from 100 GBP studies. Overall reproducibility of data acquisition and analysis was determined in 12 patients. Mean value and standard deviation of differences between repeat studies (average time interval 27 min) were 0.8% and 4.3% EF units, respectively, (r = 0.98). We conclude that left-ventricular EF can be computed automatically from GBP scintigrams with minimal operator-interaction and good reproducibility; EFs are similar to those from contrast ventriculography. http://repub.eur.nl/res/pub/4073/ 1982-01-01T00:00:00Z --